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Cheng YW, Luo Y, Zheng SJ, Xiao JH. Combination therapy with human amniotic epithelial cells and hyaluronic acid promotes immune balance recovery in type 1 diabetic rats through local engraftment. Scand J Immunol 2023; 97:e13246. [PMID: 36575914 DOI: 10.1111/sji.13246] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 12/15/2022] [Accepted: 12/17/2022] [Indexed: 12/29/2022]
Abstract
Stem cell engraftment is currently a promising approach for type 1 diabetes mellitus (T1DM) treatment. In our previous study, engraftment of a combination of human amniotic epithelial cells (hAECs) and hyaluronic acid (HA) showed potent anti-diabetic effect in streptozotocin (STZ)-induced T1DM mice via tail vein injection. Here, we adopted a different route of stem cell delivery, that is via pancreatic subcapsular transplantation. This combined local engraftment of hAECs and HA in STZ-induced T1DM rats showed potent anti-diabetic activity, leading to stronger hypoglycaemia, more intact islet structure and increased number of insulin-positive cells compared with those with hAECs or insulin treatments. Engraftment of hAECs alone increased the proportion of Th1 and T-reg cells and decreased the proportion of Th2 and Th17 cells to protect islet β cells in STZ-induced T1DM rats, whereas the combined engraftment of hAECs and HA showed more potent regulatory capacity, considerably decreased the level of TNF-α and IL-17 and increased the level of TGF-β1 compared with those by other treatments. The potent synergistic effect of HA contributed to the recovery of immune balance in the diabetic rat model, thereby suggesting a new strategy for effective treatment of T1DM.
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Affiliation(s)
- Ya-Wei Cheng
- Institute of Medicinal Biotechnology, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Yi Luo
- Institute of Medicinal Biotechnology, Affiliated Hospital of Zunyi Medical University, Zunyi, China
- Zunyi Municipal Key Laboratory of Medicinal Biotechnology & Guizhou Provincial Research Center for Translational Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Shu-Juan Zheng
- Institute of Medicinal Biotechnology, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Jian-Hui Xiao
- Institute of Medicinal Biotechnology, Affiliated Hospital of Zunyi Medical University, Zunyi, China
- Zunyi Municipal Key Laboratory of Medicinal Biotechnology & Guizhou Provincial Research Center for Translational Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, China
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Padovano M, Scopetti M, Manetti F, Morena D, Radaelli D, D'Errico S, Di Fazio N, Frati P, Fineschi V. Pancreatic transplant surgery and stem cell therapy: Finding the balance between therapeutic advances and ethical principles. World J Stem Cells 2022; 14:577-586. [PMID: 36157914 PMCID: PMC9453273 DOI: 10.4252/wjsc.v14.i8.577] [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: 03/18/2022] [Revised: 05/24/2022] [Accepted: 08/01/2022] [Indexed: 02/07/2023] Open
Abstract
The latest achievements in the field of pancreas transplantation and stem cell therapy require an effort by the scientific community to clarify the ethical implications of pioneering treatments, often characterized by high complexity from a surgical point of view, due to transplantation of multiple organs at the same time or at different times, and from an immunological point of view for stem cell therapy. The fundamental value in the field of organ transplants is, of course, a solidarity principle, namely that of protecting the health and life of people for whom transplantation is a condition of functional recovery, or even of survival. The nature of this value is that of a concept to which the legal discipline of transplants entrusts its own ethical dignity and for which it has ensured a constitutional recognition in different systems. The general principle of respect for human life, both of the donor and of the recipient, evokes the need not to put oneself and one's neighbor in dangerous conditions. The present ethical reflection aims to find a balance between the latest therapeutic advances and several concepts including the idea of the person, the respect due to the dead, the voluntary nature of the donation and the consent to the same, the gratuitousness of the donation, the scientific progress and the development of surgical techniques, and the policies of health promotion.
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Affiliation(s)
- Martina Padovano
- Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Rome 00185, Italy
| | - Matteo Scopetti
- Department of Medical Surgical Sciences and Translational Medicine, Sapienza University of Rome, Rome 00189, Italy
| | - Federico Manetti
- Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Rome 00185, Italy
| | - Donato Morena
- Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Rome 00185, Italy
| | - Davide Radaelli
- Department of Medicine, Surgery and Health, University of Trieste, Trieste 34149, Italy
| | - Stefano D'Errico
- Department of Medicine, Surgery and Health, University of Trieste, Trieste 34149, Italy
| | - Nicola Di Fazio
- Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Rome 00185, Italy
| | - Paola Frati
- Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Rome 00185, Italy
| | - Vittorio Fineschi
- Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Rome 00185, Italy.
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Chen W, Jiang W, Dong J, Wang J, Wang B. MiR-200b-3p induces the formation of insulin-producing cells from umbilical cord mesenchymal stem cells by targeting ZEB2. Crit Rev Eukaryot Gene Expr 2022; 32:33-46. [DOI: 10.1615/critreveukaryotgeneexpr.2022041822] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Chitosan for biomedical applications, promising antidiabetic drug delivery system, and new diabetes mellitus treatment based on stem cell. Int J Biol Macromol 2021; 190:417-432. [PMID: 34450151 DOI: 10.1016/j.ijbiomac.2021.08.154] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Revised: 08/14/2021] [Accepted: 08/18/2021] [Indexed: 02/07/2023]
Abstract
Since chitosan's excellent pharmacokinetic and chemical properties, it is an attractive and promising carbohydrate biopolymer in biomedical applications. Chitosan's beneficial function in the defense and propagation of pancreatic β cells, reducing hyperglycemia, and avoiding diabetes mellitus associated with impaired lipid metabolism has been demonstrated in several studies. Additionally, chitosan has also been used in various nanocarriers to deliver various antidiabetic drugs to reduce glucose levels. Herein, the first to provide the currently available potential benefits of chitosan in diabetes mellitus treatment focuses on chitosan-based nanocarriers for oral administration of various antidiabetic drugs nasal and subcutaneous passages. Moreover, chitosan is used to activate and deliver stem cells and differentiate them into cells similar to pancreatic beta cells as a new type of treatment for type one diabetes mellitus. The results of this review will be helpful in the development of promising treatments and better control of diabetes mellitus.
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Tailored generation of insulin producing cells from canine mesenchymal stem cells derived from bone marrow and adipose tissue. Sci Rep 2021; 11:12409. [PMID: 34117315 PMCID: PMC8196068 DOI: 10.1038/s41598-021-91774-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Accepted: 06/01/2021] [Indexed: 12/30/2022] Open
Abstract
The trend of regenerative therapy for diabetes in human and veterinary practices has conceptually been proven according to the Edmonton protocol and animal models. Establishing an alternative insulin-producing cell (IPC) resource for further clinical application is a challenging task. This study investigated IPC generation from two practical canine mesenchymal stem cells (cMSCs), canine bone marrow-derived MSCs (cBM-MSCs) and canine adipose-derived MSCs (cAD-MSCs). The results illustrated that cBM-MSCs and cAD-MSCs contain distinct pancreatic differentiation potential and require the tailor-made induction protocols. The effective generation of cBM-MSC-derived IPCs needs the integration of genetic and microenvironment manipulation using a hanging-drop culture of PDX1-transfected cBM-MSCs under a three-step pancreatic induction protocol. However, this protocol is resource- and time-consuming. Another study on cAD-MSC-derived IPC generation found that IPC colonies could be obtained by a low attachment culture under the three-step induction protocol. Further, Notch signaling inhibition during pancreatic endoderm/progenitor induction yielded IPC colonies through the trend of glucose-responsive C-peptide secretion. Thus, this study showed that IPCs could be obtained from cBM-MSCs and cAD-MSCs through different induction techniques. Also, further signaling manipulation studies should be conducted to maximize the protocol’s efficiency.
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Sun ZY, Yu TY, Jiang FX, Wang W. Functional maturation of immature β cells: A roadblock for stem cell therapy for type 1 diabetes. World J Stem Cells 2021; 13:193-207. [PMID: 33815669 PMCID: PMC8006013 DOI: 10.4252/wjsc.v13.i3.193] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2020] [Revised: 01/19/2021] [Accepted: 02/25/2021] [Indexed: 02/06/2023] Open
Abstract
Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease caused by the specific destruction of pancreatic islet β cells and is characterized as the absolute insufficiency of insulin secretion. Current insulin replacement therapy supplies insulin in a non-physiological way and is associated with devastating complications. Experimental islet transplantation therapy has been proven to restore glucose homeostasis in people with severe T1DM. However, it is restricted by many factors such as severe shortage of donor sources, progressive loss of donor cells, high cost, etc. As pluripotent stem cells have the potential to give rise to all cells including islet β cells in the body, stem cell therapy for diabetes has attracted great attention in the academic community and the general public. Transplantation of islet β-like cells differentiated from human pluripotent stem cells (hPSCs) has the potential to be an excellent alternative to islet transplantation. In stem cell therapy, obtaining β cells with complete insulin secretion in vitro is crucial. However, after much research, it has been found that the β-like cells obtained by in vitro differentiation still have many defects, including lack of adult-type glucose stimulated insulin secretion, and multi-hormonal secretion, suggesting that in vitro culture does not allows for obtaining fully mature β-like cells for transplantation. A large number of studies have found that many transcription factors play important roles in the process of transforming immature to mature human islet β cells. Furthermore, PDX1, NKX6.1, SOX9, NGN3, PAX4, etc., are important in inducing hPSC differentiation in vitro. The absent or deficient expression of any of these key factors may lead to the islet development defect in vivo and the failure of stem cells to differentiate into genuine functional β-like cells in vitro. This article reviews β cell maturation in vivo and in vitro and the vital roles of key molecules in this process, in order to explore the current problems in stem cell therapy for diabetes.
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Affiliation(s)
- Zi-Yi Sun
- Department of Endocrinology, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361100, Fujian Province, China
| | - Ting-Yan Yu
- Department of Endocrinology, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361100, Fujian Province, China
| | - Fang-Xu Jiang
- Department of Endocrinology, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361100, Fujian Province, China
| | - Wei Wang
- Department of Endocrinology, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361100, Fujian Province, China.
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Zhang X, He J, Wang W. Progress in the use of mesenchymal stromal cells for osteoarthritis treatment. Cytotherapy 2021; 23:459-470. [PMID: 33736933 DOI: 10.1016/j.jcyt.2021.01.008] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Revised: 12/20/2020] [Accepted: 01/29/2021] [Indexed: 12/26/2022]
Abstract
LITERATURE REVIEW OF MSCS IN THE TREATMENT OF OSTEOARTHRITIS IN THE PAST FIVE YEARS: Osteoarthritis (OA) is one of the most common chronic joint diseases, with prominent symptoms caused by many factors. However, current medical interventions for OA have resulted in poor clinical outcomes, demonstrating that there are huge unmet medical needs in this area. Cell therapy has opened new avenues of OA treatment. Different sources of mesenchymal stromal cells (MSCs) may have different phenotypes and cellular functions. Pre-clinical and clinical studies have demonstrated the feasibility, safety and efficacy of MSC therapy. Mitogen-activated protein kinase, Wnt and Notch signaling pathways are involved in the chondrogenesis of MSC-mediated treatments. MSCs may also exert effective immunoregulatory and paracrine effects to stimulate tissue repair. Therapy with extracellular vesicles containing cytokines, which are secreted by MSCs, might be a potential treatment for OA.
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Affiliation(s)
- Xiaotian Zhang
- Department of Orthopedics, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Jiyin He
- Department of Orthopedics, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Wen Wang
- Clinical Development, IASO Biotherapeutics Co., Ltd., Shanghai, China.
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Yang H, Qin D, Xu S, He C, Sun J, Hua J, Peng S. Folic acid promotes proliferation and differentiation of porcine pancreatic stem cells into insulin-secreting cells through canonical Wnt and ERK signaling pathway. J Steroid Biochem Mol Biol 2021; 205:105772. [PMID: 33091596 DOI: 10.1016/j.jsbmb.2020.105772] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2020] [Revised: 09/29/2020] [Accepted: 10/04/2020] [Indexed: 11/16/2022]
Abstract
Porcine pancreatic stem cells (pPSCs) can be induced to differentiate into insulin-producing cells in vitro and thus serve as a major cells source for β-cell regeneration. However, this application is limited by the weak cell proliferation ability and low insulin induction efficiency. In this study, we explored the role of folic acid in the proliferation of pPSCs and the formation of insulin-secreting cells. We found that FA-treated pPSCs cells had a high EDU positive rate, and the proliferation marker molecules PCNA, CyclinD1 and c-Myc were up-regulated, while the expression of folate receptor α (FOLRα) was up-regulated. In further research, interference FOLRα or adding canonical Wnt signaling pathway or ERK signaling pathway inhibitors could significantly inhibit the effect of FA on pPSCs proliferation. Meanwhile, during the differentiation of pPSCs into insulin-secreting cells, we found that the maturation marker genes Insulin, NKX6.1, MafA, and NeuroD1 was upregulated in insulin-secreting cell masses differentiationed from pPSCs after FA treatment, and the functional molecules Insulin and C-peptide were increased, the ability to secrete insulin in response to high glucose was also increased. With the addition of Wnt and ERK signaling pathway inhibitors, the pro-differentiation effect of FA was weakened. In conclusion, FA promotes the proliferation of pPSCs by binding to folate receptor α (FOLRα) and increase the efficiency of directed differentiation of pPSCs into insulin-producing cells by regulating canonical Wnt and ERK signaling pathway. This study lays theoretical foundation for solving the bottleneck in the treatment of diabetes with stem cell transplantation in future.
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Affiliation(s)
- Hong Yang
- College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling, Shaanxi, 712100, PR China
| | - Dezhe Qin
- College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling, Shaanxi, 712100, PR China
| | - Shuanshuan Xu
- College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling, Shaanxi, 712100, PR China
| | - Chen He
- College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling, Shaanxi, 712100, PR China
| | - Jing Sun
- College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling, Shaanxi, 712100, PR China
| | - Jinlian Hua
- College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling, Shaanxi, 712100, PR China
| | - Sha Peng
- College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling, Shaanxi, 712100, PR China.
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Stem Cells in Clinical Research and Therapy. Stem Cells 2021. [DOI: 10.1007/978-981-16-1638-9_10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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Sun SY, Gao Y, Liu GJ, Li YK, Gao W, Ran XW. Efficacy and Safety of Stem Cell Therapy for T1DM: An Updated Systematic Review and Meta-Analysis. J Diabetes Res 2020; 2020:5740923. [PMID: 33102605 PMCID: PMC7569432 DOI: 10.1155/2020/5740923] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Revised: 07/20/2020] [Accepted: 09/17/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND The long-term insulin therapy for type 1 diabetes mellitus (T1DM) fails to achieve optimal glycemic control and avoid adverse events simultaneously. Stem cells have unique immunomodulatory capacities and have been considered as a promising interventional strategy for T1DM. Stem cell therapy in T1DM has been tried in many studies. However, the results were controversial. We thus performed a meta-analysis to update the efficacy and safety of stem cell therapy in patients with T1DM. METHODS We systematically searched the Medline, EMBASE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Web of Science, Wan Fang Data, China National Knowledge Infrastructure, VIP database, and the Chinese Biomedical Literature Database (SinoMed) for relevant studies published before March 19, 2019. The outcomes included parameters for glycemic control (i.e., glycosylated hemoglobin (HbA1c) levels and insulin dosages), β cell function (i.e., fasting C-peptide levels and area-under-curve of C-peptide concentration (AUCC)), and relative risk of adverse events. Statistical analysis was conducted by using RevMan 5.3 and Stata 12.0. RESULTS Five randomized controlled trials (RCTs) and eight nonrandomized concurrent control trials (NRCCTs) with a total of 396 individuals were finally included into the meta-analysis. Among RCTs, stem cell therapy could significantly reduce HbA1c levels (MD = -1.20, 95% CI -1.91 to -0.49, P = 0.0009) and increase fasting C-peptide levels (MD = 0.25, 95% CI 0.04 to 0.45, P = 0.02) and AUCC (SMD = 0.66, 95% CI 0.13 to 1.18, P = 0.01). Stem cell therapy could also reduce insulin dosages (SMD = -2.65, 95% CI -4.86 to -0.45, P = 0.02) at 6 months after treatment. NRCCTs also had consistent results. Furthermore, RCTs showed stem cell therapy did not increase relative risk of gastrointestinal symptom (RR = 0.69, 95% CI 0.14 to 3.28, P = 0.64) and infection (RR = 0.97, 95% CI 0.40 to 2.34, P = 0.95). However, NRCCTs showed stem cell therapy increased relative risk of gastrointestinal symptom (RR = 44.49, 95% CI 9.20 to 215.18, P < 0.00001). CONCLUSION Stem cell therapy for T1DM may improve glycemic control and β cell function without increasing the risk of serious adverse events. Stem cell therapy may also have a short-term (3-6 months) effect on reducing insulin dosages.
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Affiliation(s)
- Shi-Yi Sun
- Diabetic Foot Care Center, Department of Endocrinology and Metabolism, West China Hospital Sichuan University, Chengdu, Sichuan 610041, China
| | - Yun Gao
- Diabetic Foot Care Center, Department of Endocrinology and Metabolism, West China Hospital Sichuan University, Chengdu, Sichuan 610041, China
| | - Guan-Jian Liu
- Chinese Cochrane Centre, Chengdu, Sichuan 610041, China
| | - Yong-Kun Li
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital Sichuan University, Chengdu, Sichuan 610041, China
| | - Wei Gao
- Diabetic Foot Care Center, Department of Endocrinology and Metabolism, West China Hospital Sichuan University, Chengdu, Sichuan 610041, China
| | - Xing-Wu Ran
- Diabetic Foot Care Center, Department of Endocrinology and Metabolism, West China Hospital Sichuan University, Chengdu, Sichuan 610041, China
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Medicinal plants in the adjunctive treatment of patients with type-1 diabetes: a systematic review of randomized clinical trials. J Diabetes Metab Disord 2020; 19:1917-1929. [PMID: 33520869 DOI: 10.1007/s40200-020-00633-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Accepted: 09/08/2020] [Indexed: 12/22/2022]
Abstract
Propose This study aims to systematically review the randomized controlled trials that address the effectiveness and safety of herbal medicine in patients with type 1 diabetes. Methods The Cochrane Library (latest issue); MEDLINE (until recent); EMBASE (until recent); AMED (Allied and Complementary Medicine Database) (until recent); and CINHAL (until recent) were searched electronically for the identification of trials until October 2019. Articles were initially screened based on title and abstract and then by full text by two independent authors. References of retrieved studies were hand-searched for further studies. Risk of bias was assessed according to the Cochrane handbook of systematic reviews of interventions. The results were summarized into GRADE (grading of recommendations, assessment, development and evaluation) tables. No meta-analysis was applicable as only one study was found for each intervention. Results Four RCTs were finally included in the systematic review with an overall moderate quality of conduct and low quality of reporting. The sample sizes were very small. The results of these RCTs show that cinnamon pills and Berberine/Silymarine compound capsules may decrease blood glucose indices from baseline, while fenugreek seeds and fig leaf decoction do not show any statistically significant effect. Conclusions The evidence is scarce and no recommendations can be made based on current evidence. Further trials with more rigorous methodology and stronger quality of reporting are needed to make conclusions.
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Wu Q, Zheng S, Qin Y, Zheng X, Chen H, Yang T, Zhang M. Efficacy and safety of stem cells transplantation in patients with type 1 diabetes mellitus-a systematic review and meta-analysis. Endocr J 2020; 67:827-840. [PMID: 32321876 DOI: 10.1507/endocrj.ej20-0050] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
Stem cells (SCs) therapy is a new promising therapeutic modality for type 1 diabetes (T1DM). We performed a systematic review and meta-analysis to evaluate the efficacy and safety of stem cells transplantation (SCT) in patients with T1DM. We searched five literature databases (MEDLINE, EMBASE, Web of Science, WanFang and CENTRAL) up to 31 October 2019. 29 studies (487 patients with T1DM) were included in our meta-analysis. There was no substantial publication bias. Meta-analysis showed the SCT had significant effect to decrease HbA1c (SMD, 1.40; 95% CI, 0.93 to 1.86; p < 0.00001; I2 = 89%) and to improve C-peptide levels (SMD, -0.62; 95% CI, -1.22 to -0.02; p = 0.04; I2 = 92%) at 1 year follow-up. Subgroup analyses showed the heterogeneity level of the results was high. Significant improvement of metabolic outcomes was observed in the subgroups of mesenchymal stem cells (MSCs) combined with hematopoietic stem cells (HSCs) and HSCs. The older age showed significant association with the efficacy in HSCs subgroup. The higher GADA positive rate before treatment also significantly associated with the decrease of daily insulin requirement. The transient insulin independence rate at last follow-up was 9.6 per 100 person-years (95% CI: 5.8-13.5%). The mean length of insulin independence was 15.6 months (95% CI: 12.3-18.9). The mortality of SCT was 3.4% (95% CI: 2.1-5.5%). Therefore, SCT is an efficacious and safe method for treating patients with T1DM especially in the subgroups of MSCs + HSCs and HSCs. Well designed, double blind and randomized controlled trails with large sample size and long-term follow-up are needed for further evaluation.
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Affiliation(s)
- Qian Wu
- Department of Endocrinology, The First Affiliated Hospital with Nanjing Medical University, Nanjing Medical University, Nanjing, 210029, China
- Department of Endocrinology, Taikang Xianlin Drum Tower Hospital, Nanjing University School of Medicine, Nanjing, 210046, China
| | - Shuai Zheng
- Department of Endocrinology, The First Affiliated Hospital with Nanjing Medical University, Nanjing Medical University, Nanjing, 210029, China
| | - Yao Qin
- Department of Endocrinology, The First Affiliated Hospital with Nanjing Medical University, Nanjing Medical University, Nanjing, 210029, China
| | - Xuqin Zheng
- Department of Endocrinology, The First Affiliated Hospital with Nanjing Medical University, Nanjing Medical University, Nanjing, 210029, China
| | - Heng Chen
- Department of Endocrinology, The First Affiliated Hospital with Nanjing Medical University, Nanjing Medical University, Nanjing, 210029, China
| | - Tao Yang
- Department of Endocrinology, The First Affiliated Hospital with Nanjing Medical University, Nanjing Medical University, Nanjing, 210029, China
| | - Mei Zhang
- Department of Endocrinology, The First Affiliated Hospital with Nanjing Medical University, Nanjing Medical University, Nanjing, 210029, China
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Wartchow KM, Rodrigues L, Lissner LJ, Federhen BC, Selistre NG, Moreira A, Gonçalves CA, Sesterheim P. Insulin-producing cells from mesenchymal stromal cells: Protection against cognitive impairment in diabetic rats depends upon implant site. Life Sci 2020; 251:117587. [PMID: 32224027 DOI: 10.1016/j.lfs.2020.117587] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2020] [Revised: 03/21/2020] [Accepted: 03/22/2020] [Indexed: 12/11/2022]
Abstract
Diabetes mellitus (DM) is a serious public health problem and can cause long-term damage to the brain, resulting in cognitive impairment in these patients. Insulin therapy for type 1 DM (DM1) can achieve overall blood glucose control, but glycemic variations can occur during injection intervals, which may contribute to some complications. Among the additional therapies available for DM1 treatment is the implantation of insulin-producing cells (IPCs) to attenuate hyperglycemia and even reverse diabetes. Here, we studied the strategy of implanting IPCs obtained from mesenchymal stromal cells (MSCs) from adipose tissue, comparing two different IPC implant sites, subcapsular renal (SR) and subcutaneous (SC), to investigate their putative protection against hippocampal damage, induced by STZ, in a rat DM1 model. Both implants improved hyperglycemia and reduced the serum content of advanced-glycated end products in diabetic rats, but serum insulin was not observed in the SC group. The SC-implanted group demonstrated ameliorated cognitive impairment (evaluated by novel object recognition) and modulation of hippocampal astroglial reactivity (evaluated by S100B and GFAP). Using GFP+ cell implants, the survival of cells at the implant sites was confirmed, as well as their migration to the pancreas and hippocampus. The presence of undifferentiated MSCs in our IPC preparation may explain the peripheral reduction in AGEs and subsequent cognitive impairment recovery, mediated by autophagic depuration and immunomodulation at the hippocampus, respectively. Together, these data reinforce the importance of MSCs for use in neuroprotective strategies, and highlight the logistic importance of the subcutaneous route for their administration.
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Affiliation(s)
- Krista Minéia Wartchow
- Federal University of Rio Grande do Sul (UFRGS), Biochemistry Post-Graduate Program, Porto Alegre, Brazil
| | - Leticia Rodrigues
- Federal University of Rio Grande do Sul (UFRGS), Biochemistry Post-Graduate Program, Porto Alegre, Brazil
| | - Lílian Juliana Lissner
- Federal University of Rio Grande do Sul (UFRGS), Biochemistry Post-Graduate Program, Porto Alegre, Brazil
| | - Barbara Carolina Federhen
- Federal University of Rio Grande do Sul (UFRGS), Biochemistry Post-Graduate Program, Porto Alegre, Brazil
| | - Nicholas Guerini Selistre
- Federal University of Rio Grande do Sul (UFRGS), Biochemistry Post-Graduate Program, Porto Alegre, Brazil
| | - Aline Moreira
- Federal University of Rio Grande do Sul (UFRGS), Biochemistry Post-Graduate Program, Porto Alegre, Brazil
| | - Carlos-Alberto Gonçalves
- Federal University of Rio Grande do Sul (UFRGS), Biochemistry Post-Graduate Program, Porto Alegre, Brazil.
| | - Patrícia Sesterheim
- Institute of Cardiology of Rio Grande do Sul, Experimental Center, Porto Alegre, Brazil
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14
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Black L, Zorina T. Cell-based immunomodulatory therapy approaches for type 1 diabetes mellitus. Drug Discov Today 2020; 25:380-391. [DOI: 10.1016/j.drudis.2019.11.016] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2019] [Revised: 11/11/2019] [Accepted: 11/30/2019] [Indexed: 12/14/2022]
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15
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Reig A, Mamillapalli R, Coolidge A, Johnson J, Taylor HS. Uterine Cells Improved Ovarian Function in a Murine Model of Ovarian Insufficiency. Reprod Sci 2019; 26:1633-1639. [PMID: 31530098 PMCID: PMC6949960 DOI: 10.1177/1933719119875818] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Primary ovarian insufficiency (POI) is defined as ovarian dysfunction in women younger than 40 years. It affects 1% of the women in this age-group and can occur iatrogenically after chemotherapy. Stem cells have been used in attempt to restore ovarian function in POI. In particular, endometrial mesenchymal stem cells (eMSCs) are easily obtainable in humans and have shown great potential for regenerative medicine. Here, we studied the potential for uterine cell (UC) suspensions containing eMSCs to improve ovarian function in a murine model of chemotherapy-induced POI. Green fluorescent protein (GFP)-labeled UC or phosphate-buffered solution (PBS) was delivered intravenously after chemotherapy. There was a significant increase in oocytes production and serum anti-Müllerian hormone concentrations after 6 weeks, as well as a 19% higher body mass in UC-treated mice. Similarly, we observed an increased number of pups in mice treated with UC than in mice treated with PBS. None of the oocytes or pups incorporated GFP, suggesting that there was no contribution of these stem cells to the oocyte pool. We conclude that treatment with UC indirectly improved ovarian function in mice with chemotherapy-induced POI. Furthermore, our study suggests that endometrial stem cell therapy may be beneficial to young women who undergo ovotoxic chemotherapy.
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Affiliation(s)
- Andres Reig
- Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA
| | - Ramanaiah Mamillapalli
- Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA
| | - Alexis Coolidge
- Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA
| | - Joshua Johnson
- Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA
| | - Hugh S. Taylor
- Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA
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16
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Farooq T, Rehman K, Hameed A, Akash MSH. Stem Cell Therapy and Type 1 Diabetes Mellitus: Treatment Strategies and Future Perspectives. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2019; 1084:95-107. [PMID: 29896720 DOI: 10.1007/5584_2018_195] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Type 1 diabetes mellitus (T1DM) is classified as an autoimmune disease which progressively results in the depletion of insulin-secreting β-cells. Consequently, the insulin secretion stops leading to hyperglycemic situations within the body. Under severe conditions, it also causes multi-organ diabetes-associated dysfunctionalities notably hypercoagulability, neuropathy, nephropathy, retinopathy, and sometimes organ failures. The prevalence of this disease has been noticed about 3% that has highlighted the serious concerns for healthcare professionals around the globe. For the treatment of this disease, the cell therapy is considered as an important therapeutic approach for the replacement of damaged β-cells. However, the development of autoantibodies unfortunately reduces their effectiveness with the passage of time and finally with the recurrence of diabetes mellitus. The development of new techniques for extraction and transplantation of islets failed to support this approach due to the issues related to major surgery and lifelong dependence on immunosuppression. For T1DM, such cells are supposed to produce, store, and supply insulin to maintain glucose homeostasis. The urgent need of much-anticipated substitute for insulin-secreting β-cells directed the researchers to focus on stem cells (SCs) to produce insulin-secreting β-cells. For being more specific and targeted therapeutic approaches, SC-based strategies opened up the new horizons to cure T1DM. This cell-based therapy aimed to produce functional insulin-secreting β-cells to cure diabetes on forever basis. The intrinsic regenerative potential along with immunomodulatory abilities of SCs highlights the therapeutic potential of SC-based strategies. In this article, we have comprehensively highlighted the role of SCs to treat diabetes mellitus.
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Affiliation(s)
- Tahir Farooq
- Department of Applied Chemistry, Government College University, Faisalabad, Pakistan
| | - Kanwal Rehman
- Institute of Pharmacy, Physiology and Pharmacology, University of Agriculture, Faisalabad, Pakistan.
| | - Arruje Hameed
- Department of Biochemistry, Government College University, Faisalabad, Pakistan
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17
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Mesenchymal stem cells to treat type 1 diabetes. Biochim Biophys Acta Mol Basis Dis 2018; 1866:165315. [PMID: 30508575 DOI: 10.1016/j.bbadis.2018.10.033] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2018] [Accepted: 10/26/2018] [Indexed: 12/13/2022]
Abstract
What is clear is we are in the era of the stem cell and its potential in ameliorating human disease. Our perspective is generated from an in vivo model in a large animal that offers significant advantages (complete transplantation tolerance, large size and long life span). This review is an effort to meld our preclinical observations with others for the reader and to outline potential avenues to improve the present outlook for patients with diabetes. This effort exams the history or background of stem cell research in the laboratory and the clinic, types of stem cells, pluripotency or lack thereof based on a variety of pre-clinical investigations attempting endocrine pancreas recovery using stem cell transplantation. The focus is on the use of hematopoietic and mesenchymal stem cells. This review will also examine recent clinical experience following stem cell transplantation in patients with type 1 diabetes.
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18
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19
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Human urine-derived stem cells play a novel role in the treatment of STZ-induced diabetic mice. J Mol Histol 2018; 49:419-428. [PMID: 29675567 DOI: 10.1007/s10735-018-9772-5] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2018] [Accepted: 04/16/2018] [Indexed: 12/19/2022]
Abstract
Human urine-derived stem cells (hUSCs) are a potential stem cell source for cell therapy. However, the effect of hUSCs on glucose metabolism regulation in type 1 diabetes was not clear. Therefore, the aim of the study was to evaluate whether hUSCs have protective effect on streptozotocin (STZ)-induced diabetes. hUSCs were extracted and cultivated with a special culture medium. Flow cytometry analysis was applied to detect cell surface markers. BALB/c male nude mice were either injected with high-dose STZ (HD-STZ) or multiple low-dose STZ (MLD-STZ). Serum and pancreatic insulin were measured, islet morphology and its vascularization were investigated. hUSCs highly expressed CD29, CD73, CD90 and CD146, and could differentiate into, at least, bone and fat in vitro. Transplantation of hUSCs into HD-STZ treated mice prolonged the median survival time and improved their blood glucose, and into those with MLD-STZ improved the glucose tolerance, islet morphology and increased the serum and pancreas insulin content. Furthermore, CD31 expression increased significantly in islets of BALB/c nude mice treated with hUSCs compared to those of un-transplanted MLD-STZ mice. hUSCs could improve the median survival time and glucose homeostasis in STZ-treated mice through promoting islet vascular regeneration and pancreatic beta-cell survival.
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20
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Gamble A, Pepper AR, Bruni A, Shapiro AMJ. The journey of islet cell transplantation and future development. Islets 2018; 10:80-94. [PMID: 29394145 PMCID: PMC5895174 DOI: 10.1080/19382014.2018.1428511] [Citation(s) in RCA: 112] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2018] [Accepted: 01/12/2018] [Indexed: 02/06/2023] Open
Abstract
Intraportal islet transplantation has proven to be efficacious in preventing severe hypoglycemia and restoring insulin independence in selected patients with type 1 diabetes. Multiple islet infusions are often required to achieve and maintain insulin independence. Many challenges remain in clinical islet transplantation, including substantial islet cell loss early and late after islet infusion. Contributions to graft loss include the instant blood-mediated inflammatory reaction, potent host auto- and alloimmune responses, and beta cell toxicity from immunosuppressive agents. Protective strategies are being tested to circumvent several of these events including exploration of alternative transplantation sites, stem cell-derived insulin producing cell therapies, co-transplantation with mesenchymal stem cells or exploration of novel immune protective agents. Herein, we provide a brief introduction and history of islet cell transplantation, limitations associated with this procedure and methods to alleviate islet cell loss as a means to improve engraftment outcomes.
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Affiliation(s)
- Anissa Gamble
- Alberta Diabetes Institute, University of Alberta, Edmonton, AB, Canada
- Members of the Canadian National Transplant Research Project (CNTRP), Canada
| | - Andrew R. Pepper
- Alberta Diabetes Institute, University of Alberta, Edmonton, AB, Canada
- Clinical Islet Transplant Program, University of Alberta, Edmonton, AB, Canada
- Members of the Canadian National Transplant Research Project (CNTRP), Canada
| | - Antonio Bruni
- Alberta Diabetes Institute, University of Alberta, Edmonton, AB, Canada
- Members of the Canadian National Transplant Research Project (CNTRP), Canada
| | - A. M. James Shapiro
- Alberta Diabetes Institute, University of Alberta, Edmonton, AB, Canada
- Clinical Islet Transplant Program, University of Alberta, Edmonton, AB, Canada
- Members of the Canadian National Transplant Research Project (CNTRP), Canada
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21
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El-Ashmawy NE, Khedr EG, El-Bahrawy HA, El-Berashy SA. Effect of human umbilical cord blood-derived mononuclear cells on diabetic nephropathy in rats. Biomed Pharmacother 2017; 97:1040-1045. [PMID: 29136782 DOI: 10.1016/j.biopha.2017.10.151] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2017] [Revised: 10/25/2017] [Accepted: 10/25/2017] [Indexed: 02/02/2023] Open
Abstract
Diabetic nephropathy (DN) is damage to the kidney which can lead to chronic renal failure, eventually requiring dialysis. Diabetes mellitus is the most common cause of adult kidney failure worldwide in the developed world. The current work was designed to elucidate the effect of mononuclear cells (MNCs) injection on reverse DN in rats exposed to streptozotocin (STZ) injection compared to metformin as a known hypoglycemic drug, 40 Male rats were divided equally into 4 groups; normal control group, diabetic control group, MNCs group were diabetic rats treated with MNCs (30×106 MNCs/rat once iv dose) in the tail vein of the rat, and metformin group were diabetic rats treated with metformin (100mg/kg orally daily dose) for four weeks. The results indicated an improvement effect of MNCs and metformin on STZ-induced DN in rats, which was evidenced by significant decrease in urinary albumin/creatinine ratio, N-acetyl-β-d-glucosaminidase (NAG), urinary kidney injury molecule-1 (KIM-1), serum urea, serum creatinine and fasting blood glucose and significant increase in C- peptide level, compared to diabetic control group. Additionally MNCs treated group exhibited pronounced effects in all previous parameters compared to metformin treated group. It is proved that MNCs treatment was superior to metformin in controlling hyperglycemia, and improving renal function in diabetic rats.
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Affiliation(s)
- Nahla E El-Ashmawy
- Department of Biochemistry, Faculty of Pharmacy, Tanta University, Tanta, Egypt
| | - Eman G Khedr
- Department of Biochemistry, Faculty of Pharmacy, Tanta University, Tanta, Egypt
| | - Hoda A El-Bahrawy
- Department of Biochemistry, Faculty of Pharmacy, Tanta University, Tanta, Egypt
| | - Shimaa A El-Berashy
- Department of Biochemistry, Faculty of Pharmacy, Tanta University, Tanta, Egypt.
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22
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Thakkar UG, Vanikar AV, Trivedi HL. Stem cells: An emerging novel therapeutic for type-1 diabetes mellitus. Diabetes Res Clin Pract 2017; 130:130-132. [PMID: 28618324 DOI: 10.1016/j.diabres.2017.04.014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2017] [Revised: 03/18/2017] [Accepted: 04/10/2017] [Indexed: 01/12/2023]
Abstract
Stem cell based strategies are therapeutically potent for treating type-1 diabetes mellitus owing to their intrinsic regenerative capacity and immunomodulatory properties to arrest autoimmune β-cell destruction, preserve residual β-cell mass, facilitate endogenous regeneration, ameliorate innate/ alloimmune graft rejection, restore β-cell-specific unresponsiveness in absence of chronic immunosuppression and to reverse hyperglycemia.
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Affiliation(s)
- Umang G Thakkar
- Department of Regenerative Medicine and Stem Cell Therapy and Pediatrics, G.R. Doshi and K.M. Mehta Institute of Kidney Diseases & Research Centre (IKDRC), Dr. H.L. Trivedi Institute of Transplantation Sciences (ITS), India.
| | - Aruna V Vanikar
- Department of Regenerative Medicine and Stem Cell Therapy and Pediatrics, G.R. Doshi and K.M. Mehta Institute of Kidney Diseases & Research Centre (IKDRC), Dr. H.L. Trivedi Institute of Transplantation Sciences (ITS), India; Department of Pathology, Laboratory Medicine, Transfusion Services and Immunohematology, G.R. Doshi and K.M. Mehta Institute of Kidney Diseases & Research Centre (IKDRC), Dr. H.L. Trivedi Institute of Transplantation Sciences (ITS), India
| | - Hargovind L Trivedi
- Department of Regenerative Medicine and Stem Cell Therapy and Pediatrics, G.R. Doshi and K.M. Mehta Institute of Kidney Diseases & Research Centre (IKDRC), Dr. H.L. Trivedi Institute of Transplantation Sciences (ITS), India; Department of Nephrology and Transplantation Medicine, G.R. Doshi and K.M. Mehta Institute of Kidney Diseases & Research Centre (IKDRC), Dr. H.L. Trivedi Institute of Transplantation Sciences (ITS), India
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23
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Abram DM, Fernandes LGR, Ramos Filho ACS, Simioni PU. The modulation of enzyme indoleamine 2,3-dioxygenase from dendritic cells for the treatment of type 1 diabetes mellitus. DRUG DESIGN DEVELOPMENT AND THERAPY 2017; 11:2171-2178. [PMID: 28769554 PMCID: PMC5533566 DOI: 10.2147/dddt.s135367] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Diabetes mellitus type 1 (DM1) is an autoimmune disease in which β-cells of the pancreas islet are destroyed by T lymphocytes. Specific T cells are activated by antigen-presenting cells, mainly dendritic cells (DCs). It is already known that the regulation of tryptophan pathway in DC can be a mechanism of immunomodulation. The enzyme indoleamine 2,3-dioxygenase (IDO) is present in many cells, including DC, and participates in the metabolism of the amino acid tryptophan. Recent studies suggest the involvement of IDO in the modulation of immune response, which became more evident after the in vitro demonstration of IDO production by DC and of the ability of these cells to inhibit lymphocyte function through the control of tryptophan metabolism. Current studies on immunotherapies describe the use of DC and IDO to control the progression of the immune response that triggers DM1. The initial results obtained are promising and indicate the possibility of developing therapies for the treatment or prevention of the DM1. Clinical trials using these cells in DM1 patients represent an interesting alternative treatment. However, clinical trials are still in the initial phase and a robust group of assays is necessary.
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Affiliation(s)
- Débora Moitinho Abram
- Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas, Cidade Universitária Zeferino Vaz, Campinas, SP, Brazil
| | - Luis Gustavo Romani Fernandes
- Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas, Cidade Universitária Zeferino Vaz, Campinas, SP, Brazil.,Department of Biomedical Science, Faculty of Americana, Americana, SP, Brazil
| | | | - Patrícia Ucelli Simioni
- Department of Biomedical Science, Faculty of Americana, Americana, SP, Brazil.,Department of Genetics, Evolution and Bioagents, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, Brazil.,Department of Biochemistry and Microbiology, Institute of Biosciences, Universidade Estadual Paulista, UNESP, Rio Claro, SP, Brazil
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24
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van de Vyver M. Intrinsic Mesenchymal Stem Cell Dysfunction in Diabetes Mellitus: Implications for Autologous Cell Therapy. Stem Cells Dev 2017; 26:1042-1053. [DOI: 10.1089/scd.2017.0025] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Affiliation(s)
- Mari van de Vyver
- Division of Endocrinology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
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25
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Adipose-Derived Cell Transplantation in Systemic Sclerosis: State of the Art and Future Perspectives. JOURNAL OF SCLERODERMA AND RELATED DISORDERS 2016. [DOI: 10.5301/jsrd.5000222] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Systemic sclerosis (SSc) is one of the most complex connective tissue diseases. Although significant progress in the knowledge of pathogenic mechanisms and timely diagnosis, therapeutic options remain limited. The attempt to find new treatments for SSc has led researchers to investigate the potential of cellular therapies using autologous and allogeneic stem cells. Multipotent mesenchymal stromal cells (MSCs) are considered an attractive candidate for cell-based therapies. MSCs comprise a heterogeneous population of cells with multilineage differentiation potential that are preferentially able to home to the sites of damage, and secrete various cytokines and growth factors that can have immunomodulatory, angiogenic, anti-inflammatory and anti-apoptotic effects. MSCs from bone-marrow have been first extensively characterized. Adipose tissue represents an additional abundant and accessible source of stem cells. Compared with BM-MSCs, adipose-derived stromal/stem cells (ASCs) offer several advantages, including ease of isolation, less donor morbidity, relative abundance, and rapidity of expansion. For all these reasons, at present ASCs are one of the most attractive and promising sources of adult stem cells for cell therapy, finding a field of application in the treatment of SSc, too. This review will focus on the current applications and possible future perspectives of adipose tissue-cell therapies in SSc.
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26
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Williams JK, Andersson KE. Regenerative pharmacology: recent developments and future perspectives. Regen Med 2016; 11:859-870. [DOI: 10.2217/rme-2016-0108] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
This review focuses on the current status of research that utilizes the application of pharmacological sciences to accelerate, optimize and characterize the development, maturation and function of bioengineered and regenerating tissues. These regenerative pharmacologic approaches have been applied to diseases of the urogenital tract, the heart, the brain, the musculoskeletal system and diabetes. Approaches have included the use of growth factors (such as VEGF and chemokines (stromal-derived factor – CXCL12) to mobilize cell to the sights of tissue loss or damage. The promise of this approach is to bypass the lengthy and expensive processes of cell isolation and implant fabrication to stimulate the body to heal itself with its own tissue regenerative pathways.
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Affiliation(s)
- James Koudy Williams
- Wake Forest Institute for Regenerative Medicine, Wake Forest Baptist Medical Center, Winston-Salem, NC 27101, USA
| | - Karl-Erik Andersson
- Wake Forest Institute for Regenerative Medicine, Wake Forest Baptist Medical Center, Winston-Salem, NC 27101, USA
- Institute for Clinical Medicine, Aarhus University, Aarhus, Denmark
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