|
1
|
Ahmad GV, Nouri S, Mohammad Gholian A, Abdollahi E, Ghorbaninezhad F, Tahmasebi S, Eterafi M, Askari MR, Safarzadeh E. Breaking barriers: CAR-NK cell therapy breakthroughs in female-related cancers. Biomed Pharmacother 2025; 187:118071. [PMID: 40253831 DOI: 10.1016/j.biopha.2025.118071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2025] [Revised: 04/04/2025] [Accepted: 04/17/2025] [Indexed: 04/22/2025] Open
Abstract
Cancer stands as a leading cause of mortality globally. The main female-related malignancies are breast cancer, with 2.3 million new cases annually, and ovarian cancer, with 300,000 new cases per year worldwide. The current treatments like surgery, chemotherapy, and radiation therapy have presumably had deficiencies in sustaining long-term anti-tumor responses. Cellular immunotherapy, also referred to as adoptive cell therapy, has shown encouraging advances by employing genetically modified immune cells in fighting cancer by engineering chimeric antigen receptors (CARs) mainly on T cells and natural killer (NK) cells. Studies in NK cell therapies involve unmodified NK cells and CAR-NK cell therapies, targeting cancer cells while limiting the destruction of normal cells. CAR-NK cells represent the next generation of therapeutic immune cells that have been shown to eliminate malignancies through CAR-dependent and CAR-independent mechanisms. They also represent possible candidates for "off-the-shelf" therapies due to their advantages, including the ability to target cancer cells independently of the major histocompatibility complex, reduced risk of alloreactivity, and fewer severe toxicities compared to CAR-T cells. To date, there have been no comprehensive review studies examining the therapeutic potential of CAR-NK cell therapy specifically for female-related malignancies, such as breast and ovarian cancers. This review offers a thorough exploration of CAR-NK cell therapy in relation to these cancers and their responses to treatment.
Collapse
Affiliation(s)
- Ghorbani Vanan Ahmad
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Cancer Immunology and Immunotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Samaneh Nouri
- Cancer Immunology and Immunotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
| | | | - Eileen Abdollahi
- Students Research Committee, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Farid Ghorbaninezhad
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Cancer Immunology and Immunotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Safa Tahmasebi
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Cancer Immunology and Immunotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Majid Eterafi
- Cancer Immunology and Immunotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Mohammad Reza Askari
- Students Research Committee, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Elham Safarzadeh
- Cancer Immunology and Immunotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran; Department of Microbiology, Parasitology, and Immunology, Ardabil University of Medical Sciences, Ardabil, Iran.
| |
Collapse
|
|
2
|
Wen YC, Wang YL, Pai LN, Yang SH, Chang TY, Chen SH, Jaing TH. Word-of-mouth referrals between patients are a critical component of medical tourism for pediatric hematopoietic cell transplantation. Medicine (Baltimore) 2025; 104:e41244. [PMID: 39792744 PMCID: PMC11730650 DOI: 10.1097/md.0000000000041244] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2024] [Accepted: 12/19/2024] [Indexed: 01/12/2025] Open
Abstract
The increasing popularity of medical tourism has sparked interest from policymakers, researchers, and the media. Factors influencing medical tourism include service quality, availability, economics, and cultural differences. This study aims to analyze the key factors that influence destination selection for medical tourists. We conducted a thorough examination of hematopoietic cell transplantation (HCT) data from the pediatric population at our institution from 2006 onwards, focusing on the aspect of medical tourism. Most connections to services were made through encounters in patients' daily lives and environments, such as word-of-mouth (WOM) from previously treated patients, family, or friends; connection through other services; referral from health care professionals; and seeing the service in their neighborhood. The results of our study indicate that the outcomes of these patients were comparable to those of patients with unrelated donor HCT who were not from an international background. Approximately 55% of our patients were referred to those who previously received treatment. Effective WOM referrals between patients are essential to the success of a medical tourism business. Patients referred to hospitals tend to have higher satisfaction rates and are more likely to become repeat customers. This ultimately leads to increased revenue and a stronger reputation in the industry. Additionally, positive feedback from satisfied patients can significantly enhance an organization's reputation and attract more potential clients. Chinese tourists and Taiwanese people share language and history. Engaging in direct conversations with physicians regarding personal matters has proven to be more effective than depending on the translator. WOM referrals are critical components of the medical tourism industry. The results indicate that WOM referrals play an essential role in conveying patients' experiences, leading to increased revenue and a stronger reputation in the industry.
Collapse
Affiliation(s)
- Yu-Chuan Wen
- Department of Nursing, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Yi-Lun Wang
- Division of Hematology/Oncology, Department of Pediatrics, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan
| | - Lan-Ni Pai
- Department of Nursing, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Shu-Ho Yang
- Department of Nursing, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Tsung-Yen Chang
- Division of Hematology/Oncology, Department of Pediatrics, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan
| | - Shih-Hsiang Chen
- Division of Hematology/Oncology, Department of Pediatrics, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan
| | - Tang-Her Jaing
- Division of Hematology/Oncology, Department of Pediatrics, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan
| |
Collapse
|
|
3
|
Wang J, Li X, Liu P, Dai Y, Zhu H, Zhang Y, Wu M, Yao Y, Liu M, Yu S, Jiang F, Wang S, Mu H, Jiao B, Yan H, Wu W, Shen Y, Li J, Wang S, Ren R. A phase 2 pilot study of umbilical cord blood infusion as an adjuvant consolidation therapy in elderly patients with acute myeloid leukemia. Signal Transduct Target Ther 2024; 9:358. [PMID: 39702351 DOI: 10.1038/s41392-024-02065-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Revised: 10/21/2024] [Accepted: 11/13/2024] [Indexed: 12/21/2024] Open
Abstract
Acute myeloid leukemia (AML) is an aging-related malignancy, with patients aged ≥60 years old facing significantly poorer prognosis. Umbilical cord blood (UCB) has emerged as a promising source with effective anti-aging roles. Here, we conducted a prospective, phase 2, single-arm trial of UCB infusion as an adjuvant consolidation therapy in elderly AML patients (ChiCTR-OPC-15006492). A total of 51 patients were enrolled (median age 66 years; range, 60-75) and received two cycles of consolidation chemotherapy combined with UCB infusion. At a median follow-up of 27.3 months (range, 9.3-100), the median overall survival (OS) was not yet reached and the median event-free survival (EFS) was 72.2 months (range, 5.4-100). The 2-year OS and EFS rates were 76.9% and 62.8%, respectively. No acute graft-versus-host disease (aGVHD) or toxicity-related death occurred in any patient. The median times to platelet and neutrophil recovery were 11.5 days (range, 6-17) and 12.2 days (range, 0-21), respectively. Single-cell RNA sequencing (scRNA-seq) identified enhanced anti-tumor and anti-aging properties of UCB, manifested through activation of immune responses and telomere synthesis/maintenance. These findings suggest that UCB infusion is an effective and safe post-remission adjuvant therapy for elderly AML patients. This study provides evidence that anti-aging therapy may serve as a new and promising dimension in combined cancer treatment.
Collapse
Affiliation(s)
- Jinzeng Wang
- Shanghai Institute of Hematology, State Key Laboratory for Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Xiaoyang Li
- Shanghai Institute of Hematology, State Key Laboratory for Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Ping Liu
- Shanghai Institute of Hematology, State Key Laboratory for Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Yao Dai
- Shanghai Institute of Hematology, State Key Laboratory for Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Hongming Zhu
- Shanghai Institute of Hematology, State Key Laboratory for Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Yunxiang Zhang
- Shanghai Institute of Hematology, State Key Laboratory for Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Min Wu
- Shanghai Institute of Hematology, State Key Laboratory for Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Yunying Yao
- Shanghai Institute of Hematology, State Key Laboratory for Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Mingzhu Liu
- Shanghai Institute of Hematology, State Key Laboratory for Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Shuting Yu
- Shanghai Institute of Hematology, State Key Laboratory for Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Fangying Jiang
- Shanghai Institute of Hematology, State Key Laboratory for Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Shuai Wang
- Shanghai Institute of Hematology, State Key Laboratory for Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Haoran Mu
- Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Bo Jiao
- Shanghai Institute of Hematology, State Key Laboratory for Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Hua Yan
- Shanghai Institute of Hematology, State Key Laboratory for Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
- Department of General Practice, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Wen Wu
- Shanghai Institute of Hematology, State Key Laboratory for Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Yang Shen
- Shanghai Institute of Hematology, State Key Laboratory for Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Junming Li
- Shanghai Institute of Hematology, State Key Laboratory for Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
| | - Shengyue Wang
- Shanghai Institute of Hematology, State Key Laboratory for Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
| | - Ruibao Ren
- Shanghai Institute of Hematology, State Key Laboratory for Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
- Collaborative Innovation Center of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
- International Center for Aging and Cancer, Hainan Medical University, Haikou, Hainan Province, 571199, China.
| |
Collapse
|
|
4
|
Mayani H. Umbilical Cord Blood Hematopoietic Cells: From Biology to Hematopoietic Transplants and Cellular Therapies. Arch Med Res 2024; 55:103042. [PMID: 39003965 DOI: 10.1016/j.arcmed.2024.103042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Revised: 06/13/2024] [Accepted: 07/03/2024] [Indexed: 07/16/2024]
Abstract
Umbilical cord blood (UCB) is a rich source of hematopoietic stem and progenitor cells that are biologically superior to their adult counterparts. UCB cells can be stored for several years without compromising their numbers or function. Today, public and private UCB banks have been established in several countries around the world. After 35 years since the first UCB transplant (UCBT), more than 50,000 UCBTs have been performed worldwide. In pediatric patients, UCBT is comparable to or superior to bone marrow transplantation. In adult patients, UCB can be an alternative source of hematopoietic cells when an HLA-matched unrelated adult donor is not available and when a transplant is urgently needed. Delayed engraftment (due to reduced absolute numbers of hematopoietic cells) and higher costs have led many medical institutions not to consider UCB as a first-line cell source for hematopoietic transplants. As a result, the use of UCB as a source of hematopoietic stem and progenitor cells for transplantation has declined over the past decade. Several approaches are being investigated to make UCBTs more efficient, including improving the homing capabilities of primitive UCB cells and increasing the number of hematopoietic cells to be infused. Several of these approaches have already been applied in the clinic with promising results. UCB also contains immune effector cells, including monocytes and various lymphocyte subsets, which, together with stem and progenitor cells, are excellent candidates for the development of cellular therapies for hematological and non-hematological diseases.
Collapse
Affiliation(s)
- Hector Mayani
- Oncology Research Unit, National Medical Center, Mexican Institute of Social Security, Mexico City, Mexico.
| |
Collapse
|
|
5
|
Ghaedrahmati F, Esmaeil N, Akbari V, Ashrafi F. More balance toward activating receptors and cytotoxic activity of NK cells ex vivo differentiated from human umbilical cord blood-derived CD34 + stem cells in comparison with peripheral blood NK cells. Heliyon 2024; 10:e35509. [PMID: 39170467 PMCID: PMC11336728 DOI: 10.1016/j.heliyon.2024.e35509] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Revised: 07/30/2024] [Accepted: 07/30/2024] [Indexed: 08/23/2024] Open
Abstract
Adoptive immunotherapies that use functional NK cells depend on the availability of sufficient numbers of these cells. We expanded umbilical cord blood (UCB)-CD34+ HSCs for 2 weeks and then differentiated them into NK cells and compared their function to peripheral blood (PB) NK cells. We assessed NKG2D, NKG2A, NKp30, NKp44, NKp46, and the expression of CD107a, CD57, CD69, FasL, PD-1, and IFN-γ level in two groups after co-culture with K562 cell line. We found that UCB-CD34+-derived NK cells express significantly more NKG2D, NKp44, and NKp46 receptors than PB NK cells. PB NK cells expressed significantly higher NKG2A and CD57 than UCB-CD34+-derived NK cells. In addition, UCB-CD34+-derived NK cells significantly expressed CD107a more than PB NK cells. Based on our findings, UCB-CD34+ cells can be a potentially advantageous source with strong cytotoxic function to produce allogeneic NK cells for adoptive cancer immunotherapy.
Collapse
Affiliation(s)
- Farhoodeh Ghaedrahmati
- Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Nafiseh Esmaeil
- Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
- Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Vajihe Akbari
- Department of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Farzaneh Ashrafi
- Department of Hematology Oncology, Isfahan University of Medical Sciences, Isfahan, Iran
| |
Collapse
|
|
6
|
Robinson CR, Habib A, Klomjit N, Cao Q, Holtan SG. Nephrons and non-relapse mortality: simplified comorbidity index and acute kidney injury are associated with NRM in adults undergoing allogeneic hematopoietic cell transplant. FRONTIERS IN TRANSPLANTATION 2024; 3:1352413. [PMID: 38993762 PMCID: PMC11235361 DOI: 10.3389/frtra.2024.1352413] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Accepted: 03/06/2024] [Indexed: 07/13/2024]
Abstract
The Simplified Comorbidity Index (SCI) is a recently published 5-component, pre-transplant tool to predict non-relapse mortality (NRM) in allogeneic hematopoietic cell transplantation (alloHCT) patients. The SCI captures chronic kidney disease (CKD) using estimated glomerular filtration rate (eGFR) based on the CKD-EPI equation (KDIGO 2021 CKD-EPI), which may be more sensitive to predict risk of NRM than the creatinine cut-off in the 16-component, Hematopoietic Cell Transplant-Comorbidity Index (HCT-CI). We retrospectively assessed the ability of the SCI to risk-stratify patients and the impact of acute kidney injury (AKI) to NRM in adults who underwent alloHCT at the University of Minnesota. We included 373 patients who underwent their first alloHCT between 2015 and 2019. Through multivariate analysis, we found that patients with an SCI of greater than 4 had a higher risk of NRM. Additionally, we noted that AKIs stages 2-3 prior to day +100 was independently associated with a 3-fold greater NRM than patients who did not experience clinically significant AKI.
Collapse
Affiliation(s)
- Clark Raymond Robinson
- Division of Hematology and Oncology, University of Texas Southwestern Medical Center, Dallas, TX, United States
| | - Alma Habib
- Department of Hematology, The Ohio State University, Columbus, OH, United States
| | - Nattawat Klomjit
- Division of Nephrology and Hypertension, University of Minnesota, Minneapolis, MN, United States
| | - Qing Cao
- Biostatistics and Bioinformatics, Masonic Cancer Center, University of Minnesota, Minneapolis, MN, United States
| | - Shernan Grace Holtan
- Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis, MN, United States
| |
Collapse
|
|
7
|
Guo F, Zhang Y, Cui J. Manufacturing CAR-NK against tumors: Who is the ideal supplier? Chin J Cancer Res 2024; 36:1-16. [PMID: 38455373 PMCID: PMC10915637 DOI: 10.21147/j.issn.1000-9604.2024.01.01] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Accepted: 01/12/2024] [Indexed: 03/09/2024] Open
Abstract
Chimeric antigen receptor-natural killer (CAR-NK) cells have emerged as another prominent player in the realm of tumor immunotherapy following CAR-T cells. The unique features of CAR-NK cells make it possible to compensate for deficiencies in CAR-T therapy, such as the complexity of the manufacturing process, clinical adverse events, and solid tumor challenges. To date, CAR-NK products from different allogeneic sources have exhibited remarkable anti-tumor effects on preclinical studies and have gradually been applied in clinical practice. However, each source has advantages and disadvantages. Selecting a suitable source may help maximize CAR-NK cell efficacy and increase the feasibility of clinical transformation. Therefore, this review discusses the development and challenges of CAR-NK cells from different sources to provide a reference for future exploration.
Collapse
Affiliation(s)
- Feifei Guo
- The First Hospital of Jilin University, Cancer Center, Changchun 133021, China
| | - Yi Zhang
- The First Hospital of Jilin University, Cancer Center, Changchun 133021, China
| | - Jiuwei Cui
- The First Hospital of Jilin University, Cancer Center, Changchun 133021, China
| |
Collapse
|
|
8
|
Hussain MS, Chaturvedi V. The Present Condition of Sickle Cell Disease: An Overview of Stem Cell Transplantation as a Cure. PHARMACEUTICAL FRONTS 2023; 05:e57-e63. [DOI: 10.1055/s-0043-1768918] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/06/2024] Open
Abstract
AbstractTreatment of sickle cell disease (SCD) remains largely palliative. While it can enhance living standards, persons having SCD still suffer from extreme sickling crises, end-organ destruction, and reduced life expectancy. Increasing research has resulted in the recognition and advancement of stem cell transplantation and gene therapy as possible solutions for SCDs. However, there have been various factors that have hindered their clinical application. The more advantageous of the two, stem cell transplantation, is constrained by a small donor pool, transplant difficulties, and eligibility requirements. The current article reviewed the literature on SCDs, current treatment options, and more particularly the progress of stem cell transplants. It outlined various challenges of stem cell transplant and proposed ways to increase the donor pool using alternative strategies and modifications of regimen conditioning with minimal transplant-related toxicities and associated complications.
Collapse
Affiliation(s)
- Md. Sadique Hussain
- School of Pharmaceutical Sciences, Jaipur National University, Jaipur, Rajasthan, India
| | - Varunesh Chaturvedi
- School of Pharmaceutical Sciences, Jaipur National University, Jaipur, Rajasthan, India
| |
Collapse
|
|
9
|
Ghaedrahmati F, Esmaeil N, Abbaspour M. Targeting immune checkpoints: how to use natural killer cells for fighting against solid tumors. Cancer Commun (Lond) 2022; 43:177-213. [PMID: 36585761 PMCID: PMC9926962 DOI: 10.1002/cac2.12394] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2022] [Revised: 10/08/2022] [Accepted: 11/15/2022] [Indexed: 01/01/2023] Open
Abstract
Natural killer (NK) cells are unique innate immune cells that mediate anti-viral and anti-tumor responses. Thus, they might hold great potential for cancer immunotherapy. NK cell adoptive immunotherapy in humans has shown modest efficacy. In particular, it has failed to demonstrate therapeutic efficiency in the treatment of solid tumors, possibly due in part to the immunosuppressive tumor microenvironment (TME), which reduces NK cell immunotherapy's efficiencies. It is known that immune checkpoints play a prominent role in creating an immunosuppressive TME, leading to NK cell exhaustion and tumor immune escape. Therefore, NK cells must be reversed from their dysfunctional status and increased in their effector roles in order to improve the efficiency of cancer immunotherapy. Blockade of immune checkpoints can not only rescue NK cells from exhaustion but also augment their robust anti-tumor activity. In this review, we discussed immune checkpoint blockade strategies with a focus on chimeric antigen receptor (CAR)-NK cells to redirect NK cells to cancer cells in the treatment of solid tumors.
Collapse
Affiliation(s)
- Farhoodeh Ghaedrahmati
- Department of ImmunologySchool of MedicineIsfahan University of Medical SciencesIsfahanIran
| | - Nafiseh Esmaeil
- Department of ImmunologySchool of MedicineIsfahan University of Medical SciencesIsfahanIran,Research Institute for Primordial Prevention of Non‐Communicable DiseaseIsfahan University of Medical SciencesIsfahanIran
| | - Maryam Abbaspour
- Department of Pharmaceutical BiotechnologyFaculty of PharmacyIsfahan University of Medical SciencesIsfahanIran
| |
Collapse
|
|
10
|
Lu Y, Xiong M, Sun RJ, Zhang JP, Zhao YL, Wei ZJ, Cao XY, Zhou JR, Liu DY, Lu DP. Comparisons of unmanipulated haploidentical donor, unrelated cord blood donor and matched unrelated donor hematopoietic stem cell transplantation in pediatric acquired severe aplastic anemia: a single center study. Leuk Lymphoma 2022; 63:3307-3316. [PMID: 36067518 DOI: 10.1080/10428194.2022.2118527] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
We retrospectively analyzed the outcomes of 240 pediatric SAA patients who underwent unmanipulated alternative HSCT between September 2012 and November 2020 at our center. The incidence of GF (PGF + SGF) was higher in the UCBD cohort compared to the MUD and HID cohorts [(13.5% ± 6.5%) vs (0%), and (1.6% ± 5.3%), respectively, p = .0001]. The incidence of platelet engraftment within 180 days post-HSCT was lower in the UCBD cohort (82.4% ± 2.3%) compared to the HID group (96.2% ± 1.3%) and the MUD group (97.4% ± 0.5%) (p = .020). the median duration time for platelet engraftment in the UCBD cohort was 29 days, longer than in HID cohort 14 days and the MUD cohort 13 days (p = .005). UCBD cohort had a lower 3-year failure-free survival (FFS) (70.5% ± 8.4%) compared to the HID cohort (81.1% ± 4.3%) and the MUD cohort (92.5% ± 3.1%) (p = .030) and lower 3-year GVHD/relapse free survival (GRFS) (63.3% ± 9.5.4%) compared to the HID cohort (75.5% ± 6.8%) and MUD cohort (87.9% ± 4.5%) (p = .002). UCBD-HSCT had inferior FFS and GRFS compared to an HSCT with an HID or MUD in pediatric patients with acquired SAA. A UCBD-HSCT had a higher GF and lower incidence of platelet engraftment and longer platelet engraftment time.
Collapse
Affiliation(s)
- Yue Lu
- Department of Bone Marrow Transplantation, Hebei Yanda Lu Daopei Hospital, Langfang, China
| | - Min Xiong
- Department of Bone Marrow Transplantation, Hebei Yanda Lu Daopei Hospital, Langfang, China
| | - Rui-Juan Sun
- Department of Bone Marrow Transplantation, Hebei Yanda Lu Daopei Hospital, Langfang, China
| | - Jian-Ping Zhang
- Department of Bone Marrow Transplantation, Hebei Yanda Lu Daopei Hospital, Langfang, China
| | - Yan-Li Zhao
- Department of Bone Marrow Transplantation, Hebei Yanda Lu Daopei Hospital, Langfang, China
| | - Zhi-Jie Wei
- Department of Bone Marrow Transplantation, Hebei Yanda Lu Daopei Hospital, Langfang, China
| | - Xing-Yu Cao
- Department of Bone Marrow Transplantation, Hebei Yanda Lu Daopei Hospital, Langfang, China
| | - Jia-Rui Zhou
- Department of Bone Marrow Transplantation, Hebei Yanda Lu Daopei Hospital, Langfang, China
| | - De-Yan Liu
- Department of Bone Marrow Transplantation, Hebei Yanda Lu Daopei Hospital, Langfang, China
| | - Dao-Pei Lu
- Department of Bone Marrow Transplantation, Hebei Yanda Lu Daopei Hospital, Langfang, China
| |
Collapse
|
|
11
|
Cord Blood-Derived Natural Killer Cell Exploitation in Immunotherapy Protocols: More Than a Promise? Cancers (Basel) 2022; 14:cancers14184439. [PMID: 36139598 PMCID: PMC9496735 DOI: 10.3390/cancers14184439] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Revised: 08/25/2022] [Accepted: 09/09/2022] [Indexed: 11/30/2022] Open
Abstract
Simple Summary NK cell anti-tumor activity against hematological malignancies is well-established and many studies support their role in the control of solid tumor growth and metastasis generation. However, tumor microenvironment may affect NK cell function. Ongoing studies are aimed to design novel immunotherapeutic protocols to combine NK cell-based immunotherapy with other therapeutic strategies to improve the anti-tumor NK cell response. In this context, UCB is one of the main sources of both mature NK cells and of CD34+ HSPC that can generate NK cells, both in-vivo and in-vitro. UCB-derived NK cells represent a valuable tool to perform in-vitro and preclinical analyses and are already used in several clinical settings, particularly against hematological malignancies. The present review describes the characteristics of different types of UCB-derived NK cells and the in-vitro models to expand them, both for research and clinical purposes in the context of cancer immunotherapy. Abstract In the last 20 years, Natural Killer (NK) cell-based immunotherapy has become a promising approach to target various types of cancer. Indeed, NK cells play a pivotal role in the first-line defense against tumors through major histocompatibility complex-independent immunosurveillance. Their role in the control of leukemia relapse has been clearly established and, moreover, the presence of NK cells in the tumor microenvironment (TME) generally correlates with good prognosis. However, it has also been observed that, often, NK cells poorly infiltrate the tumor tissue, and, in TME, their functions may be compromised by immunosuppressive factors that contribute to the failure of anti-cancer immune response. Currently, studies are focused on the design of effective strategies to expand NK cells and enhance their cytotoxic activity, exploiting different cell sources, such as peripheral blood (PB), umbilical cord blood (UCB) and NK cell lines. Among them, UCB represents an important source of mature NK cells and CD34+ Hematopoietic Stem and Progenitor Cells (HSPCs), as precursors of NK cells. In this review, we summarize the UCB-derived NK cell activity in the tumor context, review the different in-vitro models to expand NK cells from UCB, and discuss the importance of their exploitation in anti-tumor immunotherapy protocols.
Collapse
|
|
12
|
Murata M, Kawabe K, Hatta T, Maeda S, Fujita M. Current status of umbilical cord blood storage and provision to private biobanks by institutions handling childbirth in Japan. BMC Med Ethics 2022; 23:92. [PMID: 36096840 PMCID: PMC9465943 DOI: 10.1186/s12910-022-00830-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Accepted: 09/02/2022] [Indexed: 11/25/2022] Open
Abstract
Background The Act Regarding the Promotion of the Appropriate Supply of Hematopoietic Stem Cells for Transplant regulates only how public banks store and provide umbilical cord blood (UCB) for research or transplantation. Japan had no laws to regulate how the private banks manage the procedures, harvesting, preparation, and storage of such blood. As a result, the status of UCB distribution remains unknown. We conducted a survey to investigate the current status of UCB storage and provision to private biobanks by Japanese institutions that handle childbirth. Methods Questionnaire forms were mailed to 3,277 facilities handling childbirth that were registered in the Japan Council for Quality Health Care website. Results Of the 1,192 institutions handling childbirth that participated in the survey (response rate: 36.7%), 34.4% responded that they currently provide UCB to private biobanks, while 16.1% of facilities did so in the past. Moreover, some institutions currently provide or formerly provided UCB to medical treatment facilities (2.6%), research institutions (5.9%), companies (2.2%), or overseas treatment facilities, research institutions, or companies (0.3%). A certain number of institutions handling childbirth did not even provide explanations or obtain consent when the UCB was harvested from private bank users. Conclusions This is the first study to determine the status of UCB provision to private banks by Japanese institutions handling childbirth. Future studies will need to examine in detail how institutions handling childbirth provide explanations to private bank users and UCB providers as well as how these institutions obtain consent. Supplementary Information The online version contains supplementary material available at 10.1186/s12910-022-00830-8.
Collapse
Affiliation(s)
- Maho Murata
- Course for Health Care Management and Public Health, Graduate School of Health Management, Keio University, 4411 Endo, Fujisawa-shi, Kanagawa, 252-0882, Japan
| | - Kenichiro Kawabe
- Course for Health Care Management and Public Health, Graduate School of Health Management, Keio University, 4411 Endo, Fujisawa-shi, Kanagawa, 252-0882, Japan
| | - Taichi Hatta
- Graduate School of Public Health, Shizuoka Graduate University of Public Health, Aoi-ku, Shizuoka, 420-0881, Japan
| | - Shoichi Maeda
- Course for Health Care Management and Public Health, Graduate School of Health Management, Keio University, 4411 Endo, Fujisawa-shi, Kanagawa, 252-0882, Japan
| | - Misao Fujita
- Uehiro Research Division for iPS Cell Ethics, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan. .,Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan.
| |
Collapse
|
|
13
|
Upadhyay TK, Trivedi R, Khan F, Pandey P, Sharangi AB, Goel H, Saeed M, Park MN, Kim B. Potential Therapeutic Role of Mesenchymal-Derived Stem Cells as an Alternative Therapy to Combat COVID-19 through Cytokines Storm. Cells 2022; 11:2686. [PMID: 36078094 PMCID: PMC9455060 DOI: 10.3390/cells11172686] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Revised: 08/20/2022] [Accepted: 08/25/2022] [Indexed: 01/08/2023] Open
Abstract
Medical health systems continue to be challenged due to newly emerging COVID-19, and there is an urgent need for alternative approaches for treatment. An increasing number of clinical observations indicate cytokine storms to be associated with COVID-19 severity and also to be a significant cause of death among COVID-19 patients. Cytokine storm involves the extensive proliferative and hyperactive activity of T and macrophage cells and the overproduction of pro-inflammatory cytokines. Stem cells are the type of cell having self-renewal properties and giving rise to differentiated cells. Currently, stem cell therapy is an exciting and promising therapeutic approach that can treat several diseases that were considered incurable in the past. It may be possible to develop novel methods to treat various diseases by identifying stem cells' growth and differentiation factors. Treatment with mesenchymal stem cells (MSCs) in medicine is anticipated to be highly effective. The present review article is organized to put forward the positive arguments and implications in support of mesenchymal stem cell therapy as an alternative therapy to cytokine storms, to combat COVID-19. Using the immunomodulatory potential of the MSCs, it is possible to fight against COVID-19 and counterbalance the cytokine storm.
Collapse
Affiliation(s)
- Tarun Kumar Upadhyay
- Department of Biotechnology, Parul Institute of Applied Sciences and Animal Cell Culture and Immunobiochemistry Lab, Centre of Research for Development, Parul University, Vadodara 391760, India
| | - Rashmi Trivedi
- Department of Biotechnology, Parul Institute of Applied Sciences and Animal Cell Culture and Immunobiochemistry Lab, Centre of Research for Development, Parul University, Vadodara 391760, India
| | - Fahad Khan
- Department of Biotechnology, Noida Institute of Engineering & Technology, Greater Noida 201306, India
| | - Pratibha Pandey
- Department of Biotechnology, Noida Institute of Engineering & Technology, Greater Noida 201306, India
| | - Amit Baran Sharangi
- Department of Plantation, Spices, Medicinal & Aromatic Crops, BCKV-Agricultural University, Mohanpur 741252, India
| | - Harsh Goel
- Department of Laboratory Oncology, All India Institute of Medical Sciences, New Delhi 110023, India
| | - Mohd Saeed
- Department of Biology, College of Sciences, University of Hail, Hail 34464, Saudi Arabia
| | - Moon Nyeo Park
- Department of Korean Medicine, Kyung Hee University, Seoul 05254, Korea
| | - Bonglee Kim
- Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea
| |
Collapse
|
|
14
|
Mild or Moderate COVID-19 during Pregnancy Does Not Affect the Content of CD34+ Hematopoietic Stem Cells in Umbilical Cord Blood of Newborns. Bull Exp Biol Med 2022; 173:523-528. [PMID: 36063300 PMCID: PMC9441840 DOI: 10.1007/s10517-022-05575-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Indexed: 11/29/2022]
Abstract
The study included umbilical cord blood samples (n=64) intended for cryogenic storage of hematopoietic stem cells and obtained from patients with a history of mild and moderate forms of COVID-19 during pregnancy. The control group was composed of samples (n=746) obtained from healthy women in labor. A comparative analysis of the volume of cord blood collected, the total leukocyte count, the relative and absolute content of cells with the CD34+/CD45+ phenotype revealed no significant differences between the groups.
Collapse
|
|
15
|
Rahnama R, Christodoulou I, Bonifant CL. Gene-Based Natural Killer Cell Therapies for the Treatment of Pediatric Hematologic Malignancies. Hematol Oncol Clin North Am 2022; 36:745-768. [PMID: 35773048 PMCID: PMC10158845 DOI: 10.1016/j.hoc.2022.03.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Pediatric blood cancers are among the most common malignancies that afflict children. Intensive chemotherapy is not curative in many cases, and novel therapies are urgently needed. NK cells hold promise for use as immunotherapeutic effectors due to their favorable safety profile, intrinsic cytotoxic properties, and potential for genetic modification that can enhance specificity and killing potential. NK cells can be engineered to express CARs targeting tumor-specific antigens, to downregulate inhibitory and regulatory signals, to secrete cytokine, and to optimize interaction with small molecule engagers. Understanding NK cell biology is key to designing immunotherapy for clinical translation.
Collapse
|
|
16
|
Panero AJ, Hirahara AM, Podesta L, Jamali AA, Andersen W, Smith AA. Allograft Tissues. ATLAS OF INTERVENTIONAL ORTHOPEDICS PROCEDURES 2022:89-101. [DOI: 10.1016/b978-0-323-75514-6.00008-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
|
|
17
|
Yang Y, Gergis U, Carabasi M, Filicko-O'Hara J, Wagner JL, O'Hara W, Binder A, Alpdogan O, Martinez-Outschoorn U, Porcu P, Flomenberg N, Grosso D. The Two-Step Allogeneic Stem Cell Transplant Approach Results in Rapid Engraftment and Excellent Outcomes in Patients with Lymphoid Malignancies. Transplant Cell Ther 2021; 28:159.e1-159.e5. [PMID: 34954295 DOI: 10.1016/j.jtct.2021.12.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2021] [Revised: 11/24/2021] [Accepted: 12/17/2021] [Indexed: 11/24/2022]
Abstract
The two-step graft engineering approach has been the main platform for allogeneic hematopoietic cell transplantation (allo-HCT) at Thomas Jefferson University since 2005. We have previously described separating donor lymphocytes infusion followed by cyclophosphamide for bidirectional tolerization from CD34-selected hematopoietic grafts in haploidentical and matched related donors. We analyzed 60 patients with high-risk lymphoid malignancies who underwent a two-step allo-HCT from 2008-2020. The majority of patients received haploidentical (82%) and (20%) patients received matched related stem cell grafts. Patients underwent transplant for DLBCL (n = 17, 28%), CLL (n = 10, 17%), follicular lymphoma (n=8, 13%), and Hodgkin lymphoma (n = 7, 12%). Eight patients (13%) had prior high dose chemotherapy. Thirty patients (50%) had HCT-CI ≥ 3; 20 patients (33%) had CIBMTR RDRI high or very high-risk disease. The median age for the group was 56 years (range 24-75). Neutrophils engrafted at a median of 11 days (range from 9 to 16 days) and platelets engrafted at a median of 16 days (range from 13 to 37 days). With a median follow up of six years, the 3-year probability of overall survival and disease-free survival were 62.9% (95% confidence interval is 49.3% to 73.8%) and 60.2% (95% confidence interval is 46.4% to 71.6%) respectively. The cumulative incidence of relapse at 3 years was 11.9% (confidence interval 0.052-0.216). The cumulative incidence of non-relapse mortality at 3 years was 30.1% (confidence interval 0.191-0.420). The cumulative incidence of grade 2-4 acute GVHD at one year was 45% (95% confidence interval 0.322 to 0.570). The cumulative incidence of grade 3-4 acute GVHD at one year was 5% (95% confidence interval 0.013 to 0.126). The cumulative incidence of cGVHD at 3 years was 15.2% (95% confidence interval 0.075 to 0.254). In conclusion, the two-step approach achieved excellent outcomes in high-risk lymphoid malignancies with rapid neutrophil and platelet recovery.
Collapse
Affiliation(s)
- Yang Yang
- Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Usama Gergis
- Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
| | - Matthew Carabasi
- Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Joanne Filicko-O'Hara
- Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - John L Wagner
- Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - William O'Hara
- Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Adam Binder
- Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Onder Alpdogan
- Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Ubaldo Martinez-Outschoorn
- Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Pierluigi Porcu
- Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Neal Flomenberg
- Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Dolores Grosso
- Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania
| |
Collapse
|
|
18
|
Single nucleotide polymorphisms within HLA region are associated with the outcomes of unrelated cord blood transplantation. Sci Rep 2021; 11:21925. [PMID: 34753965 PMCID: PMC8578435 DOI: 10.1038/s41598-021-01155-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Accepted: 10/15/2021] [Indexed: 11/15/2022] Open
Abstract
Cord blood transplantation (CBT) provides a treatment scheme for hematologic diseases and leukemia in both children and adults. However, adverse reactions and transplantation-related death may still occur in patients receiving CBT even when donor and recipient have fully matched HLA in high-resolution HLA typing analysis. Single nucleotide polymorphisms (SNPs) of HLA-related and unrelated genes are known to associate with disease status of patients with unrelated stem cell transplantation. In this study, the genomic regions ranging from 500 base pairs upstream to 500 base pairs downstream of the eight SNPs that were reported as transplantation determinants by Petersdorf et al. were analyzed to evaluate whether genetic variants were associated with the survival status of patients, and the risk for severe (grades 3–4) graft-versus-host disease (GVHD) or cytomegalovirus (CMV) infection/reactivation. The analyses were performed in the mode of recipient genotype, donor genotype, and recipient-donor mismatching, respectively. By analysis of sixty-five patients and their HLA-matched unrelated donors, we found that five SNPs were associated with patient survival which included the recipient genotype with SNPs of rs107822 in the RING1 gene, and rs2070120, rs17220087 and rs17213693 in the HLA-DOB gene; and the recipient-donor mismatching with SNPs of rs9282369 in HLA-DOA gene, and rs2070120, rs17220087 and rs17213693 in the HLA-DOB gene. Five SNPs were associated with the risk for severe GVHD which included the donor genotype with SNPs of rs213210 and rs2523675; the recipient genotype with SNPs of rs9281491 in the HCP5 gene; and the recipient-donor mismatching with SNPs of rs209130 in the TRIM27 gene, and rs986522 in the COL11A2 gene. Six SNPs were related to the risk for CMV infection/reactivation which included the donor genotype with SNPs of rs435766, rs380924, and rs2523957; and the recipient-donor mismatching with SNPs of rs2070120, rs17220087, and rs17213693 in the HLA-DOB gene; and rs435766 and rs380924 in the MICD gene. This study provides the basis for larger analyses and if the results are confirmed, a way of selecting better unrelated CBT candidate donors.
Collapse
|
|
19
|
Jahan S, Kaushal R, Pasha R, Pineault N. Current and Future Perspectives for the Cryopreservation of Cord Blood Stem Cells. Transfus Med Rev 2021; 35:95-102. [PMID: 33640254 DOI: 10.1016/j.tmrv.2021.01.003] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Revised: 01/22/2021] [Accepted: 01/24/2021] [Indexed: 12/29/2022]
Abstract
Hematopoietic stem cell (HSC) transplantation is a well-established procedure for the treatment of many blood related malignancies and disorders. Before transplantation, HSC are collected and cryopreserved until use. The method of cryopreservation should preserve both the number and function of HSC and downstream progenitors responsible for long- and short-term engraftment, respectively. This is especially critical for cord blood grafts, since the cell number associated with this stem cell source is often limiting. Loss of function in cryopreserved cells occurs following cryoinjuries due to osmotic shock, dehydration, solution effects and mechanical damage from ice recrystallization during freezing and thawing. However, cryoinjuries can be reduced by 2 mitigation strategies; the use of cryoprotectants (CPAs) and use of control rate cooling. Currently, slow cooling is the most common method used for the cryopreservation of HSC graft. Moreover, dimethyl-sulfoxide (DMSO) and dextran are popular intracellular and extracellular CPAs used for HSC grafts, respectively. Yet, DMSO is toxic to cells and can cause significant side effects in stem cells' recipients. However, new CPAs and strategies are emerging that may soon replace DMSO. The aim of this review is to summarise key concepts in cryobiology and recent advances in the field of HSC cryobiology. Other important issues that need to be considered are also discussed such as transient warming events and thawing of HSC grafts.
Collapse
Affiliation(s)
- Suria Jahan
- Canadian Blood Services, Centre for Innovation, Ottawa, Ontario, Canada; Biochemistry, Microbiology and Immunology department, University of Ottawa, Ottawa, Ontario, Canada
| | - Richa Kaushal
- Canadian Blood Services, Centre for Innovation, Ottawa, Ontario, Canada; Biochemistry, Microbiology and Immunology department, University of Ottawa, Ottawa, Ontario, Canada
| | - Roya Pasha
- Canadian Blood Services, Centre for Innovation, Ottawa, Ontario, Canada
| | - Nicolas Pineault
- Canadian Blood Services, Centre for Innovation, Ottawa, Ontario, Canada; Biochemistry, Microbiology and Immunology department, University of Ottawa, Ottawa, Ontario, Canada.
| |
Collapse
|
|
20
|
Chowdhury S, Ghosh S. Sources, Isolation and culture of stem cells? Stem Cells 2021. [DOI: 10.1007/978-981-16-1638-9_2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
|
|
21
|
Jin YY, Yang WZ, Zou S, Sun ZY, Wu CT, Yang ZY. Chemoradiotherapy combined with NK cell transfer in a patient with recurrent and metastatic nasopharyngeal carcinoma inducing long-term tumor control: A case report. Medicine (Baltimore) 2020; 99:e22785. [PMID: 33120792 PMCID: PMC7581140 DOI: 10.1097/md.0000000000022785] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Revised: 07/14/2020] [Accepted: 09/18/2020] [Indexed: 11/26/2022] Open
Abstract
RATIONALE Nasopharyngeal carcinoma (NPC) is one of the most common malignancies in Southern China. Although combined chemotherapy with radiotherapy has been widely used in treating locally advanced lesions, relapse and metastases remain the primary cause of treatment failure, and are associated with an extremely poor prognosis. Therefore, more efficient and milder therapies are needed. PATIENT CONCERNS Herein, we report a patient with advanced NPC with intracranial metastases who showed progression during conventional treatment. DIAGNOSES Nonkeratinizing undifferentiated nasopharyngeal carcinoma (stage IV). INTERVENTIONS After the completion of initial chemoradiotherapy and targeted therapy, metastases to brain occurred during follow-up. Ex vivo-cultured allogeneic NK cell infusion was offered. OUTCOMES Although the intracranial metastases did not decrease 10 months after the NK cell treatment, they decreased significantly at 31 months after the treatment and partially disappeared. The tumor response indicated partial response. Furthermore, all of the intracranial metastases continued to decrease at about 42 months after treatment. LESSONS The brain metastases of NPC are rare with poor prognosis. Radiotherapy in NPC can disrupt the blood-brain barrier, which may contribute to the metastases of brain. This case report will provide rationale for NK cell infusion following regular chemoradiotherapy.
Collapse
Affiliation(s)
- Yuan-yuan Jin
- NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing
| | - Wen-zhuo Yang
- Sun Yat-sen University School of Medicine, Guangzhou
| | - Sen Zou
- NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing
| | - Zheng-yang Sun
- NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing
| | - Chun-tao Wu
- North China University of Science and Technology Affiliated Hospital, Tangshan, China
| | - Zhao-yong Yang
- NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing
| |
Collapse
|
|
22
|
Zhao X, Cai L, Hu Y, Wang H. Cord-Blood Natural Killer Cell-Based Immunotherapy for Cancer. Front Immunol 2020; 11:584099. [PMID: 33193399 PMCID: PMC7642255 DOI: 10.3389/fimmu.2020.584099] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2020] [Accepted: 10/02/2020] [Indexed: 12/15/2022] Open
Abstract
Natural killer (NK) cells are a predominant part of innate immune cells and play a crucial role in anti-cancer immunity. NK cells can kill target cells nonspecifically, and their recognition of target cells is not restricted by the major histocompatibility complex. NK cells also fight against tumor cells independently of antibodies and prior activation. Of note, umbilical cord blood (UCB) is a rich source of NK cells. Immunotherapies based on UCB-derived NK cells are becoming increasingly researched, and the investigations are producing encouraging results. In recent years, non-modified and modified UCB-derived NK cells have been successfully developed to fight against tumor cells. Herein, UCB-derived NK cell-based immunotherapy is a potential strategy for the treatment of cancer in the future. In this review, we focus on discussing the biological characteristics of UCB-derived NK cells and their application prospects in anti-tumor immunotherapy, including the latest preclinical and clinical researches.
Collapse
Affiliation(s)
| | | | - Yu Hu
- Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Huafang Wang
- Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| |
Collapse
|
|
23
|
Abdulrazeq F, Matsumoto MM, Abduljabbar R, Al-Hajj A, Alayash M, Ballourah R, Issak S, Issak Z. Identifying Barriers to Umbilical Cord Blood Banking in Jordan: A Cross-Sectional Survey of Obstetricians. Int J Hematol Oncol Stem Cell Res 2020; 14:213-225. [PMID: 33603982 PMCID: PMC7876430 DOI: 10.18502/ijhoscr.v14i4.4474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2019] [Accepted: 05/11/2020] [Indexed: 11/24/2022] Open
Abstract
Background: The expansion of umbilical cord blood (UCB) banking necessitates a greater understanding among obstetricians in order to responsibly inform parents about UCB collection and storage. Gaps in knowledge can compromise public UCB banking efforts and result in missed opportunities and public misguidance about UCB banking. Materials and Methods: A cross-sectional survey was disseminated among obstetricians in Amman, Jordan. The questionnaire aimed to evaluate obstetricians' knowledge of and attitude toward UCB storage and applications, as well as current practice patterns. Results: Ninety-six obstetricians responded (55% response rate), most of whom were Jordanian (71%), female (83%), resident physicians (59%), and working in either private (43%) or public (42%) hospitals, with an average of 6.5 years in practice. Only 26% had personal experience in UCB collection, and 20% had received education on UCB collection. Nearly 75% said their hospitals lacked standard operating procedures, guidelines, or infectious disease screening for UCB units. Overall knowledge about UCB was moderate, and the internet was the most common information source (54%). Overall attitudes were positive, especially in desire to expand personal knowledge about UCB, integrate information into medical residency curricula, and establish a public UCB bank in Jordan. However, many believed that ethical (61%) and religious (56%) controversies surround UCB donation. Conclusion: This study identifies deficiencies in quality control and experience in UCB collection in Jordan, as well as areas of inadequate knowledge and ethical controversies among obstetricians. These issues contribute to public misinformation and limit public UCB donation programs, and requires improved medical education on this topic.
Collapse
Affiliation(s)
- Fayez Abdulrazeq
- Community Medicine and Public Health Department, Faculty of Medicine, Yemen’s University of Science and Technology-Jordan Branch, Farid Abu Minnah Street, Amman, Jordan
| | - Monica M. Matsumoto
- Pritzker School of Medicine, University of Chicago, 924 E. 57 Street, Suite 104, Chicago, IL, 60637, USA
| | - Reem Abduljabbar
- Community Medicine and Public Health Department, Faculty of Medicine, Yemen’s University of Science and Technology-Jordan Branch, Farid Abu Minnah Street, Amman, Jordan
| | - Amira Al-Hajj
- Community Medicine and Public Health Department, Faculty of Medicine, Yemen’s University of Science and Technology-Jordan Branch, Farid Abu Minnah Street, Amman, Jordan
| | - Melad Alayash
- Community Medicine and Public Health Department, Faculty of Medicine, Yemen’s University of Science and Technology-Jordan Branch, Farid Abu Minnah Street, Amman, Jordan
| | - Rahaf Ballourah
- Community Medicine and Public Health Department, Faculty of Medicine, Yemen’s University of Science and Technology-Jordan Branch, Farid Abu Minnah Street, Amman, Jordan
| | - Sumayya Issak
- Community Medicine and Public Health Department, Faculty of Medicine, Yemen’s University of Science and Technology-Jordan Branch, Farid Abu Minnah Street, Amman, Jordan
| | - Zubeida Issak
- Community Medicine and Public Health Department, Faculty of Medicine, Yemen’s University of Science and Technology-Jordan Branch, Farid Abu Minnah Street, Amman, Jordan
| |
Collapse
|
|
24
|
Ding Y, Gao S, Shen J, Bai T, Yang M, Xu S, Gao Y, Zhang Z, Li L. TNFSF15 facilitates human umbilical cord blood haematopoietic stem cell expansion by activating Notch signal pathway. J Cell Mol Med 2020; 24:11146-11157. [PMID: 32910534 PMCID: PMC7576288 DOI: 10.1111/jcmm.15626] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Revised: 06/09/2020] [Accepted: 06/12/2020] [Indexed: 12/24/2022] Open
Abstract
The lack of efficient ex vivo expansion methods restricts clinical use of haematopoietic stem cells (HSC) for the treatment of haematological malignancies and degenerative diseases. Umbilical cord blood (UCB) serves as an alternative haematopoietic stem cell source. However, currently what limits the use of UCB‐derived HSC is the very low numbers of haematopoietic stem and progenitor cells available for transplantation in a single umbilical cord blood unit. Here, we report that TNFSF15, a member of the tumour necrosis factor superfamily, promotes the expansion of human umbilical cord blood (UCB)‐derived HSC. TNFSF15‐treated UCB‐HSC is capable of bone marrow engraftment as demonstrated with NOD/SCID or NOD/Shi‐SCID/IL2Rgnull (NOG) mice in both primary and secondary transplantation. The frequency of repopulating cells occurring in the injected tibiae is markedly higher than that in vehicle‐treated group. Additionally, signal proteins of the Notch pathway are highly up‐regulated in TNFSF15‐treated UCB‐HSC. These findings indicate that TNFSF15 is useful for in vitro expansion of UCB‐HSC for clinical applications. Furthermore, TNFSF15 may be a hopeful selection for further UCB‐HSC application or study.
Collapse
Affiliation(s)
- Yahui Ding
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, China
| | - Shan Gao
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, China
| | - Jian Shen
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, China
| | - Tairan Bai
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, China
| | - Ming Yang
- Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
| | - Shiqi Xu
- Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
| | - Yingdai Gao
- Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
| | - Zhisong Zhang
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, China
| | - Luyuan Li
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, China
| |
Collapse
|
|
25
|
Cheng YQ, Wang SB, Liu JH, Jin L, Liu Y, Li CY, Su YR, Liu YR, Sang X, Wan Q, Liu C, Yang L, Wang ZC. Modifying the tumour microenvironment and reverting tumour cells: New strategies for treating malignant tumours. Cell Prolif 2020; 53:e12865. [PMID: 32588948 PMCID: PMC7445401 DOI: 10.1111/cpr.12865] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Revised: 06/02/2020] [Accepted: 06/08/2020] [Indexed: 02/06/2023] Open
Abstract
The tumour microenvironment (TME) plays a pivotal role in tumour fate determination. The TME acts together with the genetic material of tumour cells to determine their initiation, metastasis and drug resistance. Stromal cells in the TME promote the growth and metastasis of tumour cells by secreting soluble molecules or exosomes. The abnormal microenvironment reduces immune surveillance and tumour killing. The TME causes low anti‐tumour drug penetration and reactivity and high drug resistance. Tumour angiogenesis and microenvironmental hypoxia limit the drug concentration within the TME and enhance the stemness of tumour cells. Therefore, modifying the TME to effectively attack tumour cells could represent a comprehensive and effective anti‐tumour strategy. Normal cells, such as stem cells and immune cells, can penetrate and disrupt the abnormal TME. Reconstruction of the TME with healthy cells is an exciting new direction for tumour treatment. We will elaborate on the mechanism of the TME to support tumours and the current cell therapies for targeting tumours and the TME—such as immune cell therapies, haematopoietic stem cell (HSC) transplantation therapies, mesenchymal stem cell (MSC) transfer and embryonic stem cell‐based microenvironment therapies—to provide novel ideas for producing breakthroughs in tumour therapy strategies.
Collapse
Affiliation(s)
- Ya Qi Cheng
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Shou Bi Wang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Jia Hui Liu
- Affiliated Dongguan People's Hospital, Southern Medical University, Dongguan, China
| | - Lin Jin
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Ying Liu
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Chao Yang Li
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Ya Ru Su
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Yu Run Liu
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Xuan Sang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Qi Wan
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Chang Liu
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Liu Yang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Zhi Chong Wang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| |
Collapse
|
|
26
|
Pasha R, Howell A, Turner TR, Halpenny M, Elmoazzen H, Acker JP, Pineault N. Transient warming affects potency of cryopreserved cord blood units. Cytotherapy 2020; 22:690-697. [PMID: 32591113 DOI: 10.1016/j.jcyt.2020.04.039] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Accepted: 04/04/2020] [Indexed: 10/24/2022]
Abstract
BACKGROUND AIMS Cryopreserved cord blood units (CBUs) can be exposed to transient warming events (TWEs) during routine banking operations, which may affect their potency. NetCord-FACT guidelines recommend removal of these CBUs from inventory. The objective of this work was to evaluate warming kinetics of frozen CBUs in different settings to determine the optimal working environment and define the impact of different TWE scenarios on CB post-thaw quality and potency. METHODS The warming kinetics of frozen CBUs was influenced by both working surfaces and ambient working temperature, with cold plates providing better protection than vinyl or metal surfaces. Measurement of time for required operational activities revealed that CBUs are probably exposed to core temperatures greater than -150°C even when cold plates are used to reduce warming rates. RESULTS On the basis of the warming kinetics and observed operational activities, three TWE causing scenarios (control, typical, worst case) were investigated using a pool-and-split design and cell viability, recovery and potency (colony-forming unit [CFU]) assays were performed. TWEs were found to have little impact on the recovery of total nucleated cells or on the viability of CD34+ cells. In contrast, the viability and recovery of CD45+ cells in the smaller CBU compartments were reduced by TWEs. Moreover, the worst-case TWE reduced CFU recovery from CBUs, whereas the typical-scenario TWE had little effect. CONCLUSIONS Our results demonstrate that the distal segment underestimates the viability and potency of CBUs and that TWEs can affect the post-thaw viability and potency of CBUs. Although TWEs are almost inevitable during cord-blood banking operations, their effects must be diminished by reducing exposure time, using cold plates and strict operational protocols, to prevent worst-case TWEs.
Collapse
Affiliation(s)
- Roya Pasha
- Canadian Blood Services, Centre for Innovation, Ottawa, Ontario, Canada
| | - Anita Howell
- Canadian Blood Services, Centre for Innovation, Edmonton, Alberta, Canada
| | - Tracey R Turner
- Canadian Blood Services, Centre for Innovation, Edmonton, Alberta, Canada
| | - Mike Halpenny
- Canadian Blood Services, Cord Blood Bank and Stem Cell Manufacturing, Ottawa, Canada
| | - Heidi Elmoazzen
- Canadian Blood Services, Cord Blood Bank and Stem Cell Manufacturing, Ottawa, Canada
| | - Jason P Acker
- University of Alberta, Department of Laboratory Medicine and Pathology, Edmonton, Alberta, Canada
| | - Nicolas Pineault
- University of Ottawa, Biochemistry, Microbiology and Immunology Department, Ottawa, Canada.
| |
Collapse
|
|
27
|
Poonsombudlert K, Kewcharoen J, Prueksapraopong C, Limpruttidham N. Post transplant cyclophosphamide based haplo-identical transplant versus umbilical cord blood transplant; a meta-analysis. Jpn J Clin Oncol 2020; 49:924-931. [PMID: 31265729 DOI: 10.1093/jjco/hyz099] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Revised: 06/06/2019] [Accepted: 06/12/2019] [Indexed: 01/06/2023] Open
Abstract
OBJECTIVES Both haplo-identical transplant (haplo) and umbilical cord transplant (UC) are valuable graft options for patients without available matched relative. Previous studies showed inconsistent outcomes comparing Post transplant Cyclophosphamide based haplo (PTCy-haplo) and UC; therefore, we attempt to compare the studies by mean of meta-analysis. METHODS We searched for titles of articles in MEDLINE (PubMed), Cochrane library, EMBASE database and Google scholar that compared transplantation with PTCy-haplo versus UC. We conducted a random-effect meta-analysis of seven studies involving a total of 3434 participants and reported the pooled odd ratios (OR) of acute graft-versus-host disease (aGVHD), chronic graft-versus-host disease (cGVHD), relapse and overall survival (OS) between PTCy-haplo and UC groups. RESULTS We found a significantly decreased risk of aGVHD and relapse in the PTCy-haplo group compared to the UC group with a pooled OR of 0.78, 95% Confidence Interval (CI) 0.67-0.92, I2=0%, and 0.74, 95% CI 0.57-0.97, I2=23.9% respectively. We also found a significantly increased rate of cGVHD and OS with a pooled OR of 1.41, 95% CI 1.02-1.95, I2=56.8%, and 1.77, 95% CI 1.1-2.87, I2=82.5%, respectively. CONCLUSION Our meta-analysis of clinical trials demonstrated superior outcome from PTCy-haplo group compared to the UC group in terms of decreased rate of aGVHD and relapse as well as the increased rate of OS but inferior in terms of increased cGVHD risk compared to UC transplant.
Collapse
Affiliation(s)
| | - Jakrin Kewcharoen
- University of Hawaii, internal Medicine Residency Program, Honolulu, HI, USA
| | | | - Nath Limpruttidham
- University of Hawaii, internal Medicine Residency Program, Honolulu, HI, USA
| |
Collapse
|
|
28
|
Kamal MM, Kassem DH. Therapeutic Potential of Wharton's Jelly Mesenchymal Stem Cells for Diabetes: Achievements and Challenges. Front Cell Dev Biol 2020; 8:16. [PMID: 32064260 PMCID: PMC7000356 DOI: 10.3389/fcell.2020.00016] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2019] [Accepted: 01/10/2020] [Indexed: 12/13/2022] Open
Abstract
Diabetes mellitus (DM) is an alarming metabolic disease in which insulin secreting β-cells are damaged to various extent. Unfortunately, although currently available treatments help to manage the disease, however, patients usually develop complications, as well as decreased life quality and increased mortality. Thus, efficient therapeutic interventions to treat diabetes are urgently warranted. During the past years, mesenchymal stem cells (MSCs) have made their mark as a potential weapon in various regenerative medicine applications. The main fascination about MSCs lies in their potential to exert reparative effects on an amazingly wide spectrum of tissue injury. This is further reinforced by their ease of isolation and large ex vivo expansion capacity, as well as demonstrated multipotency and immunomodulatory activities. Among all the sources of MSCs, those isolated from umbilical cord-Wharton's jelly (WJ-MSCs), have been proved to provide a great source of MSCs. WJ-MSCs do not impose any ethical concerns as those which exist regarding ESCs, and represent a readily available non-invasive source, and hence suggested to become the new gold standard for MSC-based therapies. In the current review, we shall overview achievements, as well as challenges/hurdles which are standing in the way to utilize WJ-MSCs as a novel efficient therapeutic modality for DM.
Collapse
Affiliation(s)
- Mohamed M. Kamal
- Pharmacology and Biochemistry Department, Faculty of Pharmacy, The British University in Egypt, Cairo, Egypt
- The Center for Drug Research and Development, Faculty of Pharmacy, The British University in Egypt, Cairo, Egypt
- Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
| | - Dina H. Kassem
- Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
| |
Collapse
|
|
29
|
Abstract
Since the first successful umbilical cord blood transplant in 1988, it has been estimated that more than 35,000 transplants have been performed in children and adults for the correction of inborn errors of metabolism, hematopoietic malignancies, and genetic disorders of the blood and immune system. Two types of banks have emerged for the collection and storage of umbilical cord blood: 1) public banks and 2) private banks. The benefits and limitations of public versus private umbilical cord blood banking should be reviewed with the patient because they serve different purposes. This patient discussion also should include the concept of autologous and allogeneic use of umbilical cord blood. Umbilical cord blood collected from a neonate cannot be used to treat a genetic disease or malignancy in that same individual (autologous transplant) because stored cord blood contains the same genetic variant or premalignant cells that led to the condition being treated. There is no current evidence to support the use of an autologous umbilical cord blood sample in regenerative medicine. Patients should be made aware of the quality control and regulatory organizations that provide oversight for the process of umbilical cord collection and storage. Umbilical cord blood collection should not compromise obstetric or neonatal care or alter routine practice of delayed umbilical cord clamping with the rare exception of medical indications for directed donation. Therefore, it is important to inform patients that the medical condition of the woman or neonate may prevent adequate umbilical cord blood collection. This document is updated with a statement that the routine use of private cord blood banking is not supported by available evidence and that public banking is the recommended method of obtaining cord blood. In addition, the importance of contribution from all ethnicities and races to public banks is highlighted.
Collapse
|
|
30
|
Xue A, Qian X, Gao X, Wang P, Wang L, Zheng C, Huang Z, Hu W, Shi J, Huang Y. Fecal Microbial Signatures Are Associated With Engraftment Failure Following Umbilical Cord Blood Transplantation in Pediatric Crohn's Disease Patients With IL10RA Deficiency. Front Pharmacol 2020; 11:580817. [PMID: 33162889 PMCID: PMC7580494 DOI: 10.3389/fphar.2020.580817] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Accepted: 09/17/2020] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVES Umbilical cord blood transplantation (UCBT) is associated with a relatively high rate of engraftment failure. This study aimed at exploring whether any fecal microbiota could be associated with engraftment failure following UCBT in Crohn's disease patients with IL10RA deficiency. METHODS Thirteen patients were recruited and their 230 fecal samples were collected longitudinally from immediately before conditioning chemotherapy to 8 weeks post the UCBT. The V3-V4 regions of the bacterial 16S rRNA gene were amplified by PCR and sequenced, followed by bioinformatics analyses. RESULTS Following the UCBT, 7 out of 13 patients achieved neutrophil and platelet engraftment with a median of 21 and 28 days, respectively (S group), while 6 patients failed to achieve engraftment (F group). In comparison with that in the S group, significantly lower Shannon diversity values on the UCBT day (P = 0.0176) and less abundance of Bifidobacterium longum, Bifidobacterium pseudolongum, Enterobacteriaceae_538000, and one taxon of Lachnospiraceae family was detected in the F group, accompanied by significantly higher abundances of four taxa including Lautropia, Pseudomonas, and species Microvirgula aerodenitrificans during the chemotherapy period as well as UCBT. The abundances of thirty OTUs were correlated significantly with clinical indices. CONCLUSIONS Microbial indicators of reduced diversity of microbiota and signatures of specific bacterial abundances, such as a lower abundance of Bifidobacterium longum, for engraftment failure would require validation. These indicators may help for the risk stratification in patients with IL10RA deficiency undergoing UCBT.
Collapse
Affiliation(s)
- Aijuan Xue
- Department of Gastroenterology, Children’s Hospital of Fudan University, Shanghai, China
| | - Xiaowen Qian
- Department of Hematology, Children’s Hospital of Fudan University, Shanghai, China
| | - Xuefeng Gao
- Department of Hematology-Oncology, International Cancer Center, Shenzhen University General Hospital, Shenzhen University Health Science Center, Shenzhen, China
| | - Ping Wang
- Department of Hematology, Children’s Hospital of Fudan University, Shanghai, China
| | - Lin Wang
- Department of Gastroenterology, Children’s Hospital of Fudan University, Shanghai, China
| | - Cuifang Zheng
- Department of Gastroenterology, Children’s Hospital of Fudan University, Shanghai, China
| | - Zhiheng Huang
- Department of Gastroenterology, Children’s Hospital of Fudan University, Shanghai, China
| | - Wenhui Hu
- Department of Gastroenterology, Children’s Hospital of Fudan University, Shanghai, China
| | - Jieru Shi
- Department of Gastroenterology, Children’s Hospital of Fudan University, Shanghai, China
| | - Ying Huang
- Department of Gastroenterology, Children’s Hospital of Fudan University, Shanghai, China
- *Correspondence: Ying Huang,
| |
Collapse
|
|
31
|
Li BH, Hu SY. Child with Wiskott–Aldrich syndrome underwent atypical immune reconstruction after umbilical cord blood transplantation: A case report. World J Clin Cases 2019; 7:3622-3631. [PMID: 31750346 PMCID: PMC6854412 DOI: 10.12998/wjcc.v7.i21.3622] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2019] [Revised: 07/05/2019] [Accepted: 07/20/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Timely reconstitution of a donor-derived immune system is important for recovery and long-term survival of patients after allogeneic hematopoietic stem cell transplantation (HSCT). We describe a case of Wiskott–Aldrich syndrome (WAS) treated by umbilical cord blood transplantation (UCBT) with atypical immune reconstruction.
CASE SUMMARY A 1-year-old Chinese male infant was diagnosed with WAS. WAS gene sequencing identified the mutation c.777 + 1G>A (IVS8). On August 8, 2017, he was admitted to our hospital for HSCT. We selected an unrelated Human leukocyte antigen 6/10-matched donor for UCBT. After HSCT, the immune reconstitution process was atypical, the lymphocytes reached 0.5 × 109/L on day 23, and the neutrophils reached 0.5 × 109/L on day 34. The patient’s recovery throughout the year was good.
CONCLUSION An increase in lymphocytes (especially T cells) earlier than granulocytes may be a marker of a good prognosis in UCBT.
Collapse
Affiliation(s)
- Bo-Han Li
- Department of Hematology and Oncology, Children’s Hospital of Soochow University, Suzhou 215000, Jiangsu Province, China
| | - Shao-Yan Hu
- Department of Hematology and Oncology, Children’s Hospital of Soochow University, Suzhou 215000, Jiangsu Province, China
| |
Collapse
|
|
32
|
Li BH, Hu SY. Child with Wiskott–Aldrich syndrome underwent atypical immune reconstruction after umbilical cord blood transplantation: a case report. World J Clin Cases 2019. [DOI: 10.12998/wjcc.v7.i21.3605] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
|
|
33
|
Vanegas D, Galindo CC, Páez-Gutiérrez IA, González-Acero LX, Medina-Valderrama PT, Lozano JC, Camacho-Rodríguez B, Perdomo-Arciniegas AM. Human Leukocyte Antigen and Red Blood Cells Impact Umbilical Cord Blood CD34 + Cell Viability after Thawing. Int J Mol Sci 2019; 20:E4875. [PMID: 31575081 PMCID: PMC6801469 DOI: 10.3390/ijms20194875] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Revised: 09/21/2019] [Accepted: 09/25/2019] [Indexed: 11/17/2022] Open
Abstract
Hematopoietic progenitor cell (HPC) transplantation is a treatment option for malignant and nonmalignant diseases. Umbilical cord blood (UCB) is an important HPC source, mainly for pediatric patients. It has been demonstrated that human leukocyte antigen (HLA) matching and cell dose are the most important features impacting clinical outcomes. However, UCB matching is performed using low resolution HLA typing and it has been demonstrated that the unnoticed mismatches negatively impact the transplant. Since we found differences in CD34+ viability after thawing of UCB units matched for two different patients (p = 0.05), we presumed a possible association between CD34+ cell viability and HLA. We performed a multivariate linear model (n = 67), comprising pre-cryopreservation variables and high resolution HLA genotypes separately. We found that pre-cryopreservation red blood cells (RBC), granulocytes, and viable CD34+ cell count significantly impacted CD34+ viability after thawing, along with HLA-B or -C (R2 = 0.95, p = 0.01; R2 = 0.56, p = 0.007, respectively). Although HLA-B*40:02 may have a negative impact on CD34+ cell viability, RBC depletion significantly improves it.
Collapse
Affiliation(s)
- Diana Vanegas
- Specialized researcher, Cord Blood Bank, Instituto Distrital de Ciencia, Biotecnología e Innovación en Salud. Cra. 32 # 12-81, 111611 Bogotá, Colombia.
| | - Cristian-Camilo Galindo
- Specialized researcher, Cord Blood Bank, Instituto Distrital de Ciencia, Biotecnología e Innovación en Salud. Cra. 32 # 12-81, 111611 Bogotá, Colombia.
| | - Iván-Aurelio Páez-Gutiérrez
- Specialized researcher, Cord Blood Bank, Instituto Distrital de Ciencia, Biotecnología e Innovación en Salud. Cra. 32 # 12-81, 111611 Bogotá, Colombia.
| | - Lorena-Xiomara González-Acero
- Specialized researcher, Cord Blood Bank, Instituto Distrital de Ciencia, Biotecnología e Innovación en Salud. Cra. 32 # 12-81, 111611 Bogotá, Colombia.
| | - Pavel-Tiberio Medina-Valderrama
- Specialized researcher, Cord Blood Bank, Instituto Distrital de Ciencia, Biotecnología e Innovación en Salud. Cra. 32 # 12-81, 111611 Bogotá, Colombia.
| | - Juan-Camilo Lozano
- Specialized researcher, Cord Blood Bank, Instituto Distrital de Ciencia, Biotecnología e Innovación en Salud. Cra. 32 # 12-81, 111611 Bogotá, Colombia.
| | - Bernardo Camacho-Rodríguez
- Director, Instituto Distrital de Ciencia, Biotecnología e Innovación en Salud. Cra. 32 # 12-81, 111611 Bogotá, Colombia.
| | - Ana-María Perdomo-Arciniegas
- Scientific leader, Cord Blood Bank, Instituto Distrital de Ciencia, Biotecnología e Innovación en Salud. Cra. 32 # 12-81, 111611 Bogotá, Colombia.
| |
Collapse
|
|
34
|
Kilbride P, Meneghel J, Lamb S, Morris J, Pouzet J, Jurgielewicz M, Leonforte C, Gibson D, Madrigal A. Recovery and Post-Thaw Assessment of Human Umbilical Cord Blood Cryopreserved as Quality Control Segments and Bulk Samples. Biol Blood Marrow Transplant 2019; 25:2447-2453. [PMID: 31499214 DOI: 10.1016/j.bbmt.2019.09.004] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Revised: 07/30/2019] [Accepted: 09/02/2019] [Indexed: 10/26/2022]
Abstract
Quality control (QC) segments conjoined to a bulk sample container are used to evaluate the viability and quality of cryopreserved umbilical cord blood (UCB). Such QC segments are typically attached lengths of sealed tubing that are cooled concurrently with the bulk sample, both containing material from the same donor. QC segments are thawed independently of the bulk sample to assess the quality of the cryopreserved product. In current practice, there is typically post-thaw variation between the QC segment and the bulk sample which if suggestive of inadequate performance, could lead to material being needlessly discarded. In this study, these performance differences were quantified. Two cooling protocols in common use, 1 with and 1 without a "plunge" step to induce ice nucleation, gave equivalent results that maintained the QC segment versus bulk sample differences. Ice nucleated at significantly lower temperatures in the QC segments compared with the bulk samples, a consequence of their lower volume, thereby enhancing damaging osmotic stress. A reduction in total viable cells of approximately 10% was recorded in the QC segments compared with comparable bulk samples. It has been shown that CD45+ cells are more adversely impacted by this lower ice nucleation temperature than CD34+ cells, which can result in altered composition of the post-thaw cell population.
Collapse
Affiliation(s)
- Peter Kilbride
- Asymptote, General Electric Healthcare, Cambridge, United Kingdom.
| | - Julie Meneghel
- Asymptote, General Electric Healthcare, Cambridge, United Kingdom
| | - Stephen Lamb
- Asymptote, General Electric Healthcare, Cambridge, United Kingdom
| | - John Morris
- Asymptote, General Electric Healthcare, Cambridge, United Kingdom
| | - Jerome Pouzet
- General Electric Healthcare, Biosafe SA, Eysins, Switzerland
| | - Monika Jurgielewicz
- Anthony Nolan Cell Therapy Centre, Nottingham Trent University, Nottingham, United Kingdom
| | - Christopher Leonforte
- Anthony Nolan Cell Therapy Centre, Nottingham Trent University, Nottingham, United Kingdom
| | - Daniel Gibson
- Anthony Nolan Cell Therapy Centre, Nottingham Trent University, Nottingham, United Kingdom
| | - Alejandro Madrigal
- Anthony Nolan Cell Therapy Centre, Nottingham Trent University, Nottingham, United Kingdom
| |
Collapse
|
|
35
|
Eyrich M, Schulze H. HLA Matching in Pediatric Stem Cell Transplantation. Transfus Med Hemother 2019; 46:348-355. [PMID: 31832060 DOI: 10.1159/000502422] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Accepted: 07/23/2019] [Indexed: 12/22/2022] Open
Abstract
For several malignant and nonmalignant disorders such as leukemias, lymphomas, or inborn errors of hematopoiesis, stem cell transplantation is the only curative option. Depending on the underlying cause of the disease, the conditioning regimens, source of the stem cells, and graft composition may vary. Possible stem cell donors are selected from databases considering existing major histocompatibility genes of the donor and the recipient. This is currently performed by matching human leukocyte antigen (HLA)-A, -B, and -C for class I, as well as HLA-DRB1 and -DQB1 for class II. Stem cell transplantation for nonmalignant disorders is a specialty of pediatrics. While algorithms for donor selection in these cases are generally similar, the objective of optimizing a possible graft-versus-leukemia effect is less important. In this article, we aim to provide an overview on the current methods for HLA typing and the algorithms for HLA matching. We also address ethical aspects regarding children and minors as stem cell donors.
Collapse
Affiliation(s)
- Matthias Eyrich
- University Children's Hospital, University Hospital Würzburg, Würzburg, Germany
| | - Harald Schulze
- Institute of Experimental Biomedicine, Chair I, University Hospital Würzburg, Würzburg, Germany
| |
Collapse
|
|
36
|
Patel DA, Akinsete AM, Connelly JA, Kassim AA. T-cell deplete versus T-cell replete haploidentical hematopoietic stem cell transplantation for sickle cell disease: where are we? Expert Rev Hematol 2019; 12:733-752. [DOI: 10.1080/17474086.2019.1642103] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Affiliation(s)
- Dilan A. Patel
- Department of Medicine, Division of Hematology/Oncology, Vanderbilt-Meharry Center for Excellence in Sickle Cell Disease, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Adeseye M. Akinsete
- College of Medicine, Division of Pediatric Hematology & Oncology, Lagos University Teaching Hospital, Lagos, Nigeria
| | - James A. Connelly
- Department of Pediatrics, Pediatric Hematopoietic Cell Transplant, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Adetola A. Kassim
- Department of Medicine, Division of Hematology/Oncology, Vanderbilt-Meharry Center for Excellence in Sickle Cell Disease, Vanderbilt University Medical Center, Nashville, TN, USA
| |
Collapse
|
|
37
|
Sane MS, Tang H, Misra N, Pu X, Malara S, Jones CD, Mustafi SB. Characterization of an umbilical cord blood sourced product suitable for allogeneic applications. Regen Med 2019; 14:769-789. [PMID: 31313975 DOI: 10.2217/rme-2019-0058] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Aim: Umbilical cord blood (UCB) sourced allografts are promising interventions for tissue regeneration. As applications of these allografts and regulations governing them continue to evolve, we were prompted to identify parameters determining their quality, safety and regenerative potential. Materials & methods: Flow-cytometry, mass-spectrometry, protein multiplexing, nanoparticle tracking analysis and standard biological techniques were employed. Results: Quality attributes of a uniquely processed UCB-allograft (UCBr) were enumerated based on identity (cell viability, immunophenotyping, proteomic profiling, and quantification of relevant cytokines); safety (bioburden and microbiological screening), purity (endotoxin levels) and potency (effect of UCBr on chondrocytes and mesenchymal stem cells derived exosomes). These attributes were stable up to 24 months in cryopreserved UCBr. Conclusion: We identified a comprehensive panel of tests to establish the clinical efficacy and quality control attributes of a UCB-sourced allograft.
Collapse
Affiliation(s)
- Mukta S Sane
- Department of Research & Development, Burst Biologics, Boise, ID 83705, USA
| | - Huiyuan Tang
- Department of Research & Development, Burst Biologics, Boise, ID 83705, USA
| | - Neha Misra
- Department of Research & Development, Burst Biologics, Boise, ID 83705, USA
| | - Xinzhu Pu
- Biomolecular Research Center, Boise State University, Boise, ID 83725, USA
| | - Sara Malara
- Department of Research & Development, Burst Biologics, Boise, ID 83705, USA
| | | | | |
Collapse
|
|
38
|
Wu S, Yang N, Zhong L, Luo Y, Wang H, Gong W, Zhou S, Li Y, He J, Cao H, Huang Y, Zhao Y. A novel label-free terbium(iii)-aptamer based aptasensor for ultrasensitive and highly specific detection of acute lymphoma leukemia cells. Analyst 2019; 144:3843-3852. [PMID: 31098604 DOI: 10.1039/c8an02342e] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Acute leukemia is a malignant clonal disease of hematopoietic stem cells with a high prevalence and mortality rate. However, there are no efficient tools to facilitate early diagnosis and treatment of leukemia. Therefore, development of new methods for the early diagnosis and prevention of leukemia, especially non-invasive diagnosis at the cellular level, is imperative. Here, a label-free signal-on fluorescence aptasensor based on terbium(iii)-aptamer (Tb3+-apt) was applied for the detection of leukemia. The aptamer sensitizes the fluorescence of Tb3+ and forms the strong fluorescent Tb3+-apt probe. The target cells, the T-cell acute lymphoblastic leukemia cell line (CCRF-CEM) combined with the Tb3+-apt probe to form the Tb3+-apt-CEM complex, were removed by centrifugation, and the supernatant containing a small amount of the Tb3+-apt probe was detected using a fluorescence spectrophotometer. The logarithm of cell concentration showed a good linear relationship (R2 = 0.9881) with the fluorescence signal. The linear range for CCRF-CEM detection was 5-5 × 106 cells per ml, while the detection limit was 5 cells per ml of the binding buffer. Clinical samples were collected from 100 cases, and the specificity and positive rates detected by this method were up to 94% and 90%, respectively. Therefore, a single-stranded DNA-sensitized terbium(iii) luminescence method diagnostic was developed which is rapid, sensitive, and economical and can be used for diagnosis of various types of leukemia at the early stage.
Collapse
Affiliation(s)
- Siwen Wu
- National Center for International Research of Bio-targeting Theranostics, Guangxi Key Laboratory of Bio-targeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi 530021, China.
| | - Nuo Yang
- National Center for International Research of Bio-targeting Theranostics, Guangxi Key Laboratory of Bio-targeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi 530021, China.
| | - Liping Zhong
- National Center for International Research of Bio-targeting Theranostics, Guangxi Key Laboratory of Bio-targeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi 530021, China.
| | - Yiqun Luo
- National Center for International Research of Bio-targeting Theranostics, Guangxi Key Laboratory of Bio-targeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi 530021, China.
| | - Huiling Wang
- National Center for International Research of Bio-targeting Theranostics, Guangxi Key Laboratory of Bio-targeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi 530021, China.
| | - Wenlin Gong
- National Center for International Research of Bio-targeting Theranostics, Guangxi Key Laboratory of Bio-targeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi 530021, China.
| | - Sufang Zhou
- National Center for International Research of Bio-targeting Theranostics, Guangxi Key Laboratory of Bio-targeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi 530021, China.
| | - Yanmei Li
- National Center for International Research of Bio-targeting Theranostics, Guangxi Key Laboratory of Bio-targeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi 530021, China.
| | - Jian He
- National Center for International Research of Bio-targeting Theranostics, Guangxi Key Laboratory of Bio-targeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi 530021, China.
| | - Haopei Cao
- National Center for International Research of Bio-targeting Theranostics, Guangxi Key Laboratory of Bio-targeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi 530021, China.
| | - Yong Huang
- National Center for International Research of Bio-targeting Theranostics, Guangxi Key Laboratory of Bio-targeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi 530021, China.
| | - Yongxiang Zhao
- National Center for International Research of Bio-targeting Theranostics, Guangxi Key Laboratory of Bio-targeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi 530021, China.
| |
Collapse
|
|
39
|
Cord blood research, banking, and transplantation: achievements, challenges, and perspectives. Bone Marrow Transplant 2019; 55:48-61. [PMID: 31089283 DOI: 10.1038/s41409-019-0546-9] [Citation(s) in RCA: 83] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2019] [Revised: 04/15/2019] [Accepted: 04/24/2019] [Indexed: 12/13/2022]
Abstract
The first hematopoietic transplant in which umbilical cord blood (UCB) was used as the source of hematopoietic cells was performed in October 1988. Since then, significant achievements have been reported in terms of our understanding of the biology of UCB-derived hematopoietic stem (HSCs) and progenitor (HPCs) cells. Over 40,000 UCB transplants (UCBTs) have been performed, in both children and adults, for the treatment of many different diseases, including hematologic, metabolic, immunologic, neoplastic, and neurologic disorders. In addition, cord blood banking has been developed to the point that around 800,000 units are being stored in public banks and more than 4 million units in private banks worldwide. During these 30 years, research in the UCB field has transformed the hematopoietic transplantation arena. Today, scientific and clinical teams are still working on different ways to improve and expand the use of UCB cells. A major effort has been focused on enhancing engraftment to potentially reduce risk of infection and cost. To that end, we have to understand in detail the molecular mechanisms controlling stem cell self-renewal that may lead to the development of ex vivo systems for HSCs expansion, characterize the mechanisms regulating the homing of HSCs and HPCs, and determine the relative place of UCBTs, as compared to other sources. These challenges will be met by encouraging innovative research on the basic biology of HSCs and HPCs, developing novel clinical trials, and improving UCB banking both in the public and private arenas.
Collapse
|
|
40
|
Burga RA, Khan DH, Agrawal N, Bollard CM, Fernandes R. Designing Magnetically Responsive Biohybrids Composed of Cord Blood-Derived Natural Killer Cells and Iron Oxide Nanoparticles. Bioconjug Chem 2019; 30:552-560. [PMID: 30779553 DOI: 10.1021/acs.bioconjchem.9b00048] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
We report the generation of magnetically responsive, cord blood-derived natural killer (NK) cells using iron oxide nanoparticles (IONPs). NK cells are a promising immune cell population for cancer cell therapy as they can target and lyse target tumor cells without prior education. However, NK cells cannot home to disease sites based on antigen recognition, instead relying primarily on external stimuli and chemotactic gradients for transport. Hence, we hypothesized that conjugating IONPs onto the surface of NK cells provides an added feature of magnetic homing to the NK cells, improving their therapeutic function. We describe a robust design for conjugating the IONPs onto the surface of NK cells, which maintains their intrinsic phenotype and function. The conferred magnetic-responsiveness is utilized to improve the cytolytic function of the NK cells for target cells in 2D and 3D models. These findings demonstrate the feasibility of improving NK cell homing and therapeutic efficacy with our NK:IONP "biohybrid".
Collapse
Affiliation(s)
- Rachel A Burga
- George Washington Cancer Center , George Washington University , Washington , DC 20052 , United States
| | - Daud H Khan
- Department of Bioengineering , George Mason University , Fairfax , Virginia 22030 , United States
| | - Nitin Agrawal
- Department of Bioengineering , George Mason University , Fairfax , Virginia 22030 , United States
| | - Catherine M Bollard
- George Washington Cancer Center , George Washington University , Washington , DC 20052 , United States.,Center for Cancer and Immunology Research , Children's National Health System , Washington , DC 20010 , United States
| | - Rohan Fernandes
- George Washington Cancer Center , George Washington University , Washington , DC 20052 , United States
| |
Collapse
|
|
41
|
Avgerinou G, Oikonomopoulou C, Kaisari A, Ioannidou E, Komitopoulou A, Paisou A, Tourkantoni N, Filippidou M, Kattamis A, Vessalas G, Peristeri I, Goussetis E, Kitra V. Successful long-term hematological and immunological reconstitution by autologous cord blood transplantation combined with post-transplant immunosuppression in two children with severe aplastic anemia. Pediatr Transplant 2019; 23:e13320. [PMID: 30407702 DOI: 10.1111/petr.13320] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2018] [Revised: 08/17/2018] [Accepted: 10/12/2018] [Indexed: 12/17/2022]
Abstract
aUCBT is a valuable curative option in pediatric patients with refractory idiopathic SAA and no available matched sibling or unrelated donors. Experience in the use of autologous cord blood units in patients with SAA is limited and private for-profit cord blood-banking programs are controversial. We report the successful treatment of two patients with SAA, aged 15 and 24 months, with autologous cord blood combined with immunosuppression. After conditioning with 200 mg/kg cyclophosphamide and ATG, 7.5 mg/kg, 32.2 × 107 /kg, and 3.8 × 107 /kg autologous cord blood nucleated cells were infused, respectively. One of our patients underwent transplantation after failure of IST. Both patients received post-transplant immunosuppression with cyclosporine for 12 months. They remain disease-free 6 years post-transplantation.
Collapse
Affiliation(s)
- Georgia Avgerinou
- First Department of Pediatrics, National and Kapodistrian University of Athens, Athens, Greece
| | | | - Aikaterini Kaisari
- Stem Cell Transplant Unit, Aghia Sophia Children's Hospital, Athens, Greece
| | - Elda Ioannidou
- Stem Cell Transplant Unit, Aghia Sophia Children's Hospital, Athens, Greece
| | - Anna Komitopoulou
- Stem Cell Transplant Unit, Aghia Sophia Children's Hospital, Athens, Greece
| | - Anna Paisou
- Stem Cell Transplant Unit, Aghia Sophia Children's Hospital, Athens, Greece
| | - Natalia Tourkantoni
- First Department of Pediatrics, National and Kapodistrian University of Athens, Athens, Greece
| | - Maria Filippidou
- First Department of Pediatrics, National and Kapodistrian University of Athens, Athens, Greece
| | - Antonios Kattamis
- First Department of Pediatrics, National and Kapodistrian University of Athens, Athens, Greece
| | - George Vessalas
- Stem Cell Transplant Unit, Aghia Sophia Children's Hospital, Athens, Greece
| | - Ioulia Peristeri
- Stem Cell Transplant Unit, Aghia Sophia Children's Hospital, Athens, Greece
| | - Evgenios Goussetis
- Stem Cell Transplant Unit, Aghia Sophia Children's Hospital, Athens, Greece
| | - Vasiliki Kitra
- Stem Cell Transplant Unit, Aghia Sophia Children's Hospital, Athens, Greece
| |
Collapse
|
|
42
|
Cancer Diagnostics and Therapeutics. Bioanalysis 2019. [DOI: 10.1007/978-3-030-01775-0_3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
|
|
43
|
Tan J, Lai Z, Zhong L, Zhang Z, Zheng R, Su J, Huang Y, Huang P, Song H, Yang N, Zhou S, Zhao Y. A Graphene Oxide-Based Fluorescent Aptasensor for the Turn-on Detection of CCRF-CEM. NANOSCALE RESEARCH LETTERS 2018; 13:66. [PMID: 29605867 PMCID: PMC5878827 DOI: 10.1186/s11671-017-2403-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/20/2017] [Accepted: 12/05/2017] [Indexed: 06/08/2023]
Abstract
A convenient, low-cost, and highly sensitive fluorescent aptasensor for detection of leukemia has been developed based on graphene oxide-aptamer complex (GO-apt). Graphene oxide (GO) can absorb carboxyfluorescein-labeled Sgc8 aptamer (FAM-apt) by π-π stacking and quench the fluorescence through fluorescence resonance energy transfer (FRET). In the absence of Sgc8 target cell CCRF-CEM, the fluorescence is almost all quenched. Conversely, when the CCRF-CEM cells are added, the quenched fluorescence can be recovered rapidly and significantly. Therefore, based on the change of fluorescence signals, we can detect the number of CCRF-CEM cells in a wide range from 1 × 102 to 1 × 107 cells/mL with a limit of detection (LOD) of 10 cells/mL. Therefore, this strategy of graphene oxide-based fluorescent aptasensor may be promising for the detection of cancer.
Collapse
Affiliation(s)
- Jie Tan
- National Center for International Research of Biological Targeting Diagnosis and Therapy, Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy Research, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi 530021 China
| | - Zongqiang Lai
- National Center for International Research of Biological Targeting Diagnosis and Therapy, Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy Research, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi 530021 China
| | - Liping Zhong
- National Center for International Research of Biological Targeting Diagnosis and Therapy, Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy Research, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi 530021 China
| | - Zhenghua Zhang
- National Center for International Research of Biological Targeting Diagnosis and Therapy, Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy Research, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi 530021 China
| | - Rong Zheng
- National Center for International Research of Biological Targeting Diagnosis and Therapy, Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy Research, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi 530021 China
| | - Jing Su
- National Center for International Research of Biological Targeting Diagnosis and Therapy, Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy Research, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi 530021 China
| | - Yong Huang
- National Center for International Research of Biological Targeting Diagnosis and Therapy, Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy Research, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi 530021 China
| | - Panpan Huang
- National Center for International Research of Biological Targeting Diagnosis and Therapy, Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy Research, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi 530021 China
| | - Hui Song
- National Center for International Research of Biological Targeting Diagnosis and Therapy, Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy Research, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi 530021 China
| | - Nuo Yang
- National Center for International Research of Biological Targeting Diagnosis and Therapy, Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy Research, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi 530021 China
| | - Sufang Zhou
- National Center for International Research of Biological Targeting Diagnosis and Therapy, Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy Research, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi 530021 China
| | - Yongxiang Zhao
- National Center for International Research of Biological Targeting Diagnosis and Therapy, Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy Research, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi 530021 China
| |
Collapse
|
|
44
|
Chez M, Lepage C, Parise C, Dang‐Chu A, Hankins A, Carroll M. Safety and Observations from a Placebo-Controlled, Crossover Study to Assess Use of Autologous Umbilical Cord Blood Stem Cells to Improve Symptoms in Children with Autism. Stem Cells Transl Med 2018; 7:333-341. [PMID: 29405603 PMCID: PMC5866927 DOI: 10.1002/sctm.17-0042] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2017] [Revised: 11/30/2017] [Accepted: 12/21/2017] [Indexed: 12/30/2022] Open
Abstract
The aim of this exploratory study was to assess the safety and clinical effects of autologous umbilical cord blood (AUCB) infusion in children with idiopathic autism spectrum disorder (ASD). Twenty-nine children 2 to 6 years of age with a confirmed diagnosis of ASD participated in this randomized, blinded, placebo-controlled, crossover trial. Participants were randomized to receive AUCB or placebo, evaluated at baseline, 12, and 24 weeks, received the opposite infusion, then re-evaluated at the same time points. Evaluations included assessments of safety, Expressive One Word Picture Vocabulary Test, 4th edition, Receptive One Word Picture Vocabulary Test, 4th edition, Clinical Global Impression, Stanford-Binet Fluid Reasoning and Knowledge, and the Vineland Adaptive Behavior and Socialization Subscales. Generalized linear models were used to assess the effects of the response variables at the 12- and 24-week time periods under each condition (AUCB, placebo). There were no serious adverse events. There were trends toward improvement, particularly in socialization, but there were no statistically significant differences for any endpoints. The results of this study suggest that autologous umbilical cord infusions are safe for children with ASD. Tightly controlled trials are necessary to further progress the study of AUCB for autism. Stem Cells Translational Medicine 2018;7:333-341.
Collapse
Affiliation(s)
- Michael Chez
- Pediatric NeuroscienceSacramentoCaliforniaUSA
- Sutter Institute for Medical Research (SIMR)SacramentoCaliforniaUSA
| | - Christopher Lepage
- Pediatric NeuroscienceSacramentoCaliforniaUSA
- Sutter Institute for Medical Research (SIMR)SacramentoCaliforniaUSA
| | - Carol Parise
- Sutter Institute for Medical Research (SIMR)SacramentoCaliforniaUSA
| | - Ashley Dang‐Chu
- Sutter Institute for Medical Research (SIMR)SacramentoCaliforniaUSA
| | - Andrea Hankins
- Sutter Institute for Medical Research (SIMR)SacramentoCaliforniaUSA
| | - Michael Carroll
- Bone Marrow Transplant, Sutter Medical GroupSacramentoCaliforniaUSA
| |
Collapse
|
|
45
|
Sun Z, Liu H, Luo C, Geng L, Zheng C, Tang B, Zhu X, Tong J, Wang X, Ding K, Wan X, Zhang L, Yao W, Song K, Zhang X, Wu Y, Yang H, Han Y, Liu X, Zhu W, Wu J, Wang Z. Better outcomes of modified myeloablative conditioning without antithymocyte globulin versus myeloablative conditioning in cord blood transplantation for hematological malignancies: A retrospective (development) and a prospective (validation) study. Int J Cancer 2018; 143:699-708. [PMID: 29473150 PMCID: PMC6033117 DOI: 10.1002/ijc.31339] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2017] [Revised: 01/30/2018] [Accepted: 02/02/2018] [Indexed: 01/22/2023]
Abstract
Cord blood transplantation (CBT) is an effective option for treating hematological malignancies, but graft failure (GF) remains the primary cause of therapy failure. Thus, based on myeloablative conditioning (MAC) of busulfan with cyclophosphamide (Bu/Cy) or total body irradiation with Cy (TBI/Cy), fludarabine (Flu) was added to Bu/Cy and cytarabine (CA) to TBI/Cy for a modified myeloablative conditioning (MMAC). To compare the prognosis of MMAC with MAC, we conducted a retrospective study including 58 patients who underwent CBT with MAC or MMAC from 2000 to 2011. Neutrophil and platelet engraftment rate, overall survival (OS) and disease free survival (DFS) were significantly higher in the MMAC group (adjusted hazard ratio [HR], 2.58, 2.43, 0.36 and 0.37; p < 0.01, p = 0.01, p = 0.02 and p = 0.02, separately). Nonrelapse mortality (NRM) was comparable (p = 0.183). To validate the outcomes noted in the MMAC group, we conducted a prospective single‐arm clinical trial including 188 patients who underwent CBT with MMAC from 2011 to 2015. Engraftment rate, survival and NRM of the MMAC group in the prospective trail (MMAC‐P) were similar to the MMAC group in the retrospective study (MMAC‐R). This study is the first to demonstrate the superiority of MMAC to MAC in CBT for hematological malignancies. What's new? Cord blood transplants can help patients with blood cancer, but too often, the transplant fails due to immune rejection or other problems. Typically, patients receive myeloablative conditioning (MAC) prior to CBT, but more intense regimen might improve transplant success. Here, the authors compared the success of modified myeloablative conditioning (MMAC) with conventional MAC by looking at 58 patients over an 11‐year period. They then followed up with a four‐year prospective study, including 188 patients who received cord blood transplant with MMAC. The modified conditioning regimen boosted graft success and improved survival of patients with hematological cancers.
Collapse
Affiliation(s)
- Zimin Sun
- Department of Hematology, Anhui Provincial Hospital, Anhui Medical University, Hefei, China
| | - Huilan Liu
- Department of Hematology, Anhui Provincial Hospital, Anhui Medical University, Hefei, China
| | - Chenhui Luo
- Department of Hematology, Anhui Provincial Hospital, Anhui Medical University, Hefei, China
| | - Liangquan Geng
- The First Affiliated Hospital of University of Science and Technology of China, Anhui Sheng, China
| | - Changcheng Zheng
- The First Affiliated Hospital of University of Science and Technology of China, Anhui Sheng, China
| | - Baolin Tang
- The First Affiliated Hospital of University of Science and Technology of China, Anhui Sheng, China
| | - Xiaoyu Zhu
- The First Affiliated Hospital of University of Science and Technology of China, Anhui Sheng, China
| | - Juan Tong
- The First Affiliated Hospital of University of Science and Technology of China, Anhui Sheng, China
| | - Xingbing Wang
- The First Affiliated Hospital of University of Science and Technology of China, Anhui Sheng, China
| | - Kaiyang Ding
- The First Affiliated Hospital of University of Science and Technology of China, Anhui Sheng, China
| | - Xiang Wan
- The First Affiliated Hospital of University of Science and Technology of China, Anhui Sheng, China
| | - Lei Zhang
- The First Affiliated Hospital of University of Science and Technology of China, Anhui Sheng, China
| | - Wen Yao
- The First Affiliated Hospital of University of Science and Technology of China, Anhui Sheng, China
| | - Kaiding Song
- The First Affiliated Hospital of University of Science and Technology of China, Anhui Sheng, China
| | - Xuhan Zhang
- The First Affiliated Hospital of University of Science and Technology of China, Anhui Sheng, China
| | - Yue Wu
- The First Affiliated Hospital of University of Science and Technology of China, Anhui Sheng, China
| | - Huizhi Yang
- The First Affiliated Hospital of University of Science and Technology of China, Anhui Sheng, China
| | - Yongsheng Han
- The First Affiliated Hospital of University of Science and Technology of China, Anhui Sheng, China
| | - Xin Liu
- The First Affiliated Hospital of University of Science and Technology of China, Anhui Sheng, China
| | - Weibo Zhu
- The First Affiliated Hospital of University of Science and Technology of China, Anhui Sheng, China
| | - Jingsheng Wu
- The First Affiliated Hospital of University of Science and Technology of China, Anhui Sheng, China
| | - Zuyi Wang
- The First Affiliated Hospital of University of Science and Technology of China, Anhui Sheng, China
| |
Collapse
|
|
46
|
Baron F, Ruggeri A, Beohou E, Labopin M, Sanz G, Milpied N, Michallet M, Bacigalupo A, Blaise D, Sierra J, Socié G, Cornelissen JJ, Schmid C, Giebel S, Gorin NC, Esteve J, Ciceri F, Savani BN, Mohty M, Gluckman E, Nagler A. RIC versus MAC UCBT in adults with AML: A report from Eurocord, the ALWP and the CTIWP of the EBMT. Oncotarget 2018; 7:43027-43038. [PMID: 27250025 PMCID: PMC5190005 DOI: 10.18632/oncotarget.9599] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2016] [Accepted: 05/14/2016] [Indexed: 01/08/2023] Open
Abstract
Nonrelapse mortality (NRM) is the first cause of treatment failure after unrelated cord blood transplantation (UCBT) following myeloablative conditioning (MAC). In the last decade, reduced-intensity conditioning (RIC) regimens have been developed with the aim of reducing NRM and allowing older patients and those with medical comorbidities to benefit from UCBT. The aim of the current retrospective study was to compare transplantation outcomes of acute myeloid leukemia (AML) patients given UCBT after either RIC or MAC. Data from 894 adults with AML receiving a single or double UCBT as first allograft from 2004 to 2013 at EBMT centers were included in this study. 415 patients were given UCBT after RIC while 479 patients following a MAC. In comparison to MAC recipients, RIC recipients had a similar incidence of neutrophil engraftment and of acute and chronic graft-versus-host disease (GVHD). However, RIC recipients had a higher incidence of disease relapse and a lower NRM, translating to comparable leukemia-free (LFS), GVHD-free, relapse-free survival (GRFS) and overall survival (OS). These observations remained qualitatively similar after adjusting for differences between groups in multivariate analyses. In conclusion, these data suggest that LFS and OS are similar with RIC or with MAC in adults AML patients transplanted with UCBT. These observations could serve as basis for a future prospective randomized study.
Collapse
Affiliation(s)
| | - Annalisa Ruggeri
- Eurocord, Hospital Saint Louis, AP-HP, and IUH University Paris VII, Paris, France.,AP-HP, Hématologie Clinique et Thérapie Cellulaire, Hôpital Saint-Antoine, Paris, France
| | - Eric Beohou
- EBMT Paris Office, Hospital Saint Antoine, Paris, France
| | - Myriam Labopin
- EBMT Paris Office, Hospital Saint Antoine, Paris, France
| | - Guillermo Sanz
- Hospital Universitario La Fe, Servicio de Hematologia, Valencia, Spain
| | - Noel Milpied
- CHU Bordeaux, Hématologie Clinique et Thérapie Cellulaire-Hôpital Haut-leveque, Bordeaux, France.,University of Bordeaux, Bordeaux, France
| | | | | | - Didier Blaise
- Institut Paoli Calmettes (IPC), Aix Marseille University (AMU), UM105, Centre de Recherche en Cancerologie (CRCM), Inserm U1068, CNRS UMR7258 Marseille, Marseille, France
| | - Jorge Sierra
- Hospital Santa Creu i Sant Pau, Hematology Department, Barcelona, Spain
| | - Gérard Socié
- AP-HP, Hematology Transplantation, Hospital Saint-Louis, Paris, France
| | - Jan J Cornelissen
- Erasmus Medical Center-Daniel den Hoed Cancer Center, Rotterdam, The Netherlands
| | - Christoph Schmid
- Klinikum Augsburg, Department of Hematology and Oncology, University of Munich, Augsburg, Germany
| | - Sebastian Giebel
- Maria Sklodowska-Curie Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland
| | - Norbert-Claude Gorin
- AP-HP, Hématologie Clinique et Thérapie Cellulaire, Hôpital Saint-Antoine, Paris, France.,EBMT Paris Office, Hospital Saint Antoine, Paris, France
| | - Jordi Esteve
- Deptartment of Hematology, Hospital Clinic, Barcelona, Spain
| | - Fabio Ciceri
- Department of Hematology, Ospedale San Raffaele, Università degli Studi, Milano, Italy
| | - Bipin N Savani
- Long Term Transplant Clinic, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Mohamad Mohty
- AP-HP, Hématologie Clinique et Thérapie Cellulaire, Hôpital Saint-Antoine, Paris, France.,Universite Pierre & Marie Curie, Paris, France.,INSERM, UMRS 938, Paris, France
| | - Eliane Gluckman
- Eurocord, Hospital Saint Louis, AP-HP, and IUH University Paris VII, France Monacord, Centre Scientifique de Monaco, Monaco
| | - Arnon Nagler
- EBMT Paris Office, Hospital Saint Antoine, Paris, France.,Division of Hematology and Bone Marrow Transplantation, The Chaim Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel
| |
Collapse
|
|
47
|
Gincberg G, Shohami E, Trembovler V, Alexandrovich AG, Lazarovici P, Elchalal U. Nerve growth factor plays a role in the neurotherapeutic effect of a CD45 + pan-hematopoietic subpopulation derived from human umbilical cord blood in a traumatic brain injury model. Cytotherapy 2017; 20:245-261. [PMID: 29274773 DOI: 10.1016/j.jcyt.2017.11.008] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2017] [Revised: 10/09/2017] [Accepted: 11/14/2017] [Indexed: 01/09/2023]
Abstract
BACKGROUND AIMS Human umbilical cord blood (HUCB) is an important source of stem cells for therapy of hematopoietic disorders and is a potential therapy for various neurological disorders, including traumatic brain injury (TBI). The expression of nerve growth factor (NGF) and its receptors TrkA, p75NTR and α9β1 integrin on an HUCB CD45+ pan-hematopoietic subpopulation was investigated in the context of its neurotherapeutic potential after TBI. METHODS NGF and its receptors were detected on CD45+ cells by reverse transcriptase polymerase chain reaction, flow cytometry analysis and confocal microscopy. CD45+ cells were stimulated by TBI brain extracts, and NGF levels were measured by enzyme-linked immunosorbent assay. TBI mice were divided into six groups for xenogeneic intravenous transplantation, 1 day post-trauma, with 1 × 106 CD45+ cells untreated or treated with the anti-NGF neutralizing antibody K252a, a TrkA antagonist; VLO5, an α9β1 disintegrin; or negative (vehicle) and positive (NGF) controls. RESULTS The HUCB CD45+ subpopulation constitutively expresses NGF and its receptors, mainly TrkA and p75NTR and minor levels of α9β1. In vitro experiments provided evidence that trauma-related mediators from brain extracts of TBI mice induced release of NGF from HUCB CD45+ cell cultures. HUCB CD45+ cells induced a neurotherapeutic effect in TBI mice, abrogated by cell treatment with either anti-NGF antibody or K252a, but not VLO5. CONCLUSIONS These findings strengthen the role of NGF and its TrkA receptor in the HUCB CD45+ subpopulation's neurotherapeutic effect. The presence of neurotrophin receptors in the HUCB CD45+ pan-hematopoietic subpopulation may explain the neuroprotective effect of cord blood in therapy of a variety of neurological disorders.
Collapse
Affiliation(s)
- Galit Gincberg
- School of Pharmacy Institute for Drug Research, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Esther Shohami
- School of Pharmacy Institute for Drug Research, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Victoria Trembovler
- School of Pharmacy Institute for Drug Research, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Alexander G Alexandrovich
- School of Pharmacy Institute for Drug Research, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Philip Lazarovici
- School of Pharmacy Institute for Drug Research, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
| | - Uriel Elchalal
- Department of Obstetrics and Gynecology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
| |
Collapse
|
|
48
|
Singh N, Loren AW. Overview of Hematopoietic Cell Transplantation for the Treatment of Hematologic Malignancies. Clin Chest Med 2017; 38:575-593. [DOI: 10.1016/j.ccm.2017.07.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
|
|
49
|
Hsu J, Artz A, Mayer SA, Guarner D, Bishop MR, Reich-Slotky R, Smith SM, Greenberg J, Kline J, Ferrante R, Phillips AA, Gergis U, Liu H, Stock W, Cushing M, Shore TB, van Besien K. Combined Haploidentical and Umbilical Cord Blood Allogeneic Stem Cell Transplantation for High-Risk Lymphoma and Chronic Lymphoblastic Leukemia. Biol Blood Marrow Transplant 2017; 24:359-365. [PMID: 29128555 DOI: 10.1016/j.bbmt.2017.10.040] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2017] [Accepted: 10/28/2017] [Indexed: 12/21/2022]
Abstract
Limited studies have reported on outcomes for lymphoid malignancy patients receiving alternative donor allogeneic stem cell transplants. We have previously described combining CD34-selected haploidentical grafts with umbilical cord blood (haplo-cord) to accelerate neutrophil and platelet engraftment. Here, we examine the outcome of patients with lymphoid malignancies undergoing haplo-cord transplantation at the University of Chicago and Weill Cornell Medical College. We analyzed 42 lymphoma and chronic lymphoblastic leukemia (CLL) patients who underwent haplo-cord allogeneic stem cell transplantation. Patients underwent transplant for Hodgkin lymphoma (n = 9, 21%), CLL (n = 5, 12%) and non-Hodgkin lymphomas (n = 28, 67%), including 13 T cell lymphomas. Twenty-four patients (52%) had 3 or more lines of therapies. Six (14%) and 1 (2%) patients had prior autologous and allogeneic stem cell transplant, respectively. At the time of transplant 12 patients (29%) were in complete remission, 18 had chemotherapy-sensitive disease, and 12 patients had chemotherapy-resistant disease. Seven (17%), 11 (26%), and 24 (57%) patients had low, intermediate, and high disease risk index before transplant. Comorbidity index was evenly distributed among 3 groups, with 13 (31%), 14 (33%), and 15 (36%) patients scoring 0, 1 to 2, and ≥3. Median age for the cohort was 49 years (range, 23 to 71). All patients received fludarabine/melphalan/antithymocyte globulin conditioning regimen and post-transplant graft-versus-host disease (GVHD) prophylaxis with tacrolimus and mycophenolate mofetil. The median time to neutrophil engraftment was 11 days (range, 9 to 60) and to platelet engraftment 19.5 days (range, 11 to 88). Cumulative incidence of nonrelapse mortality was 11.6% at 100 days and 19 % at one year. Cumulative incidence of relapse was 9.3% at 100 days and 19% at one year. With a median follow-up of survivors of 42 months, the 3-year rates of GVHD relapse free survival, progression-free survival, and overall survival were 53%, 62%, and 65%, respectively, for these patients. Only 8% of the survivors had chronic GVHD. In conclusion, haplo-cord transplantation offers a transplant alternative for patients with recurrent or refractory lymphoid malignancies who lack matching donors. Both neutrophil and platelet count recovery is rapid, nonrelapse mortality is limited, excellent disease control can be achieved, and the incidence of chronic GVHD is limited. Thus, haplo-cord achieves high rates of engraftment and encouraging results.
Collapse
MESH Headings
- Adult
- Aged
- Cord Blood Stem Cell Transplantation
- Graft vs Host Disease/etiology
- Graft vs Host Disease/prevention & control
- Humans
- Leukemia, Lymphocytic, Chronic, B-Cell/complications
- Leukemia, Lymphocytic, Chronic, B-Cell/mortality
- Leukemia, Lymphocytic, Chronic, B-Cell/therapy
- Lymphoma/complications
- Lymphoma/mortality
- Lymphoma/therapy
- Middle Aged
- Premedication/methods
- Survival Analysis
- Transplantation Conditioning/methods
- Transplantation, Haploidentical
- Transplantation, Homologous
- Treatment Outcome
- Young Adult
Collapse
Affiliation(s)
- Jingmei Hsu
- Department of Hematology/Oncology, Weill Cornell Medical College/New York Presbyterian Hospital, New York, New York
| | - Andrew Artz
- Section of Hematology/Oncology, University of Chicago, Chicago, Illinois
| | - Sebastian A Mayer
- Department of Hematology/Oncology, Weill Cornell Medical College/New York Presbyterian Hospital, New York, New York
| | - Danielle Guarner
- Department of Hematology/Oncology, Weill Cornell Medical College/New York Presbyterian Hospital, New York, New York
| | - Michael R Bishop
- Section of Hematology/Oncology, University of Chicago, Chicago, Illinois
| | - Ronit Reich-Slotky
- Department of Pathology, Weill Cornell Medical College/New York Presbyterian Hospital, New York, New York
| | - Sonali M Smith
- Section of Hematology/Oncology, University of Chicago, Chicago, Illinois
| | - June Greenberg
- Department of Hematology/Oncology, Weill Cornell Medical College/New York Presbyterian Hospital, New York, New York
| | - Justin Kline
- Section of Hematology/Oncology, University of Chicago, Chicago, Illinois
| | - Rosanna Ferrante
- Department of Hematology/Oncology, Weill Cornell Medical College/New York Presbyterian Hospital, New York, New York
| | - Adrienne A Phillips
- Department of Hematology/Oncology, Weill Cornell Medical College/New York Presbyterian Hospital, New York, New York
| | - Usama Gergis
- Department of Hematology/Oncology, Weill Cornell Medical College/New York Presbyterian Hospital, New York, New York
| | - Hongtao Liu
- Section of Hematology/Oncology, University of Chicago, Chicago, Illinois
| | - Wendy Stock
- Section of Hematology/Oncology, University of Chicago, Chicago, Illinois
| | - Melissa Cushing
- Department of Pathology, Weill Cornell Medical College/New York Presbyterian Hospital, New York, New York
| | - Tsiporah B Shore
- Department of Hematology/Oncology, Weill Cornell Medical College/New York Presbyterian Hospital, New York, New York
| | - Koen van Besien
- Department of Hematology/Oncology, Weill Cornell Medical College/New York Presbyterian Hospital, New York, New York.
| |
Collapse
|
|
50
|
Scaradavou A. Unrelated cord blood transplantation for non-malignant diseases: every HLA allele counts. LANCET HAEMATOLOGY 2017; 4:e307-e308. [PMID: 28668189 DOI: 10.1016/s2352-3026(17)30110-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/12/2017] [Accepted: 06/12/2017] [Indexed: 11/25/2022]
Affiliation(s)
- Andromachi Scaradavou
- National Cord Blood Program, New York Blood Center, Long Island City, New York, NY 11101, USA; Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
| |
Collapse
|