|
1
|
Teratani T, Fujimoto Y, Sakuma Y, Kasahara N, Maeda M, Miki A, Lefor AK, Sata N, Kitayama J. Improved Preservation of Rat Small Intestine Transplantation Graft by Introduction of Mesenchymal Stem Cell-Secreted Fractions. Transpl Int 2024; 37:11336. [PMID: 38962471 PMCID: PMC11219629 DOI: 10.3389/ti.2024.11336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Accepted: 06/04/2024] [Indexed: 07/05/2024]
Abstract
Segmental grafts from living donors have advantages over grafts from deceased donors when used for small intestine transplantation. However, storage time for small intestine grafts can be extremely short and optimal graft preservation conditions for short-term storage remain undetermined. Secreted factors from mesenchymal stem cells (MSCs) that allow direct activation of preserved small intestine grafts. Freshly excised Luc-Tg LEW rat tissues were incubated in preservation solutions containing MSC-conditioned medium (MSC-CM). Preserved Luc-Tg rat-derived grafts were then transplanted to wild-type recipients, after which survival, injury score, and tight junction protein expression were examined. Luminance for each graft was determined using in vivo imaging. The findings indicated that 30-100 and 3-10 kDa fractions of MSC-CM have superior activating effects for small intestine preservation. Expression of the tight-junction proteins claudin-3, and zonula occludens-1 preserved for 24 h in University of Wisconsin (UW) solution containing MSC-CM with 50-100 kDa, as shown by immunostaining, also indicated effectiveness. Reflecting the improved graft preservation, MSC-CM preloading of grafts increased survival rate from 0% to 87%. This is the first report of successful transplantation of small intestine grafts preserved for more than 24 h using a rodent model to evaluate graft preservation conditions that mimic clinical conditions.
Collapse
Affiliation(s)
- Takumi Teratani
- Division of Translational Research, Jichi Medical University, Tochigi, Japan
- Department of Surgery, Jichi Medical University, Tochigi, Japan
| | - Yasuhiro Fujimoto
- Transplantation Surgery, Nagoya University Hospital, Nagoya, Aichi, Japan
| | - Yasunaru Sakuma
- Department of Surgery, Jichi Medical University, Tochigi, Japan
| | - Naoya Kasahara
- Division of Translational Research, Jichi Medical University, Tochigi, Japan
- Department of Surgery, Jichi Medical University, Tochigi, Japan
| | - Masashi Maeda
- Division of Translational Research, Jichi Medical University, Tochigi, Japan
| | - Atsushi Miki
- Department of Surgery, Jichi Medical University, Tochigi, Japan
| | | | - Naohiro Sata
- Department of Surgery, Jichi Medical University, Tochigi, Japan
| | - Joji Kitayama
- Division of Translational Research, Jichi Medical University, Tochigi, Japan
- Department of Surgery, Jichi Medical University, Tochigi, Japan
| |
Collapse
|
|
2
|
Bilgiç T, İnce Ü, Narter F. Autologous omentum transposition for regeneration of a renal injury model in rats. Mil Med Res 2022; 9:1. [PMID: 34983664 PMCID: PMC8725455 DOI: 10.1186/s40779-021-00361-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2020] [Accepted: 12/08/2021] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND After renal trauma, surgical treatment is vital, but sometimes there may be loss of function due to fibrosis. This study aimed to evaluate the effect of autologous omentum flaps on injured renal tissues in a rat model. METHODS A total of 30 Wistar albino rats were included and randomly divided equally into a control group and four intervention groups. Iatrogenic renal injuries were repaired using a surgical technique (primary repair 1 group and primary repair 2 group) or transposition of the autologous omentum (omentum repair 1 group and omentum repair 2 group). Blood samples were taken preoperatively and on the 1st and 7th postoperative days in all groups and on the 18th postoperative day in the control and two intervention groups. All rats were sacrificed on the 7th or 18th day postoperatively, and their right kidneys were taken for histopathological evaluation. RESULTS The mean urea level significantly decreased from day 1 to day 7 and from day 1 to day 18 in the omentum repair 2 group (P = 0.005 and P = 0.004, respectively). There were no other significant changes in urea or creatinine levels within the intervention groups (P > 0.05). There was no significant correlation between the urea and creatinine levels and the histological scores (P > 0.05). The primary repair 1 and 2 groups had significantly higher median granulation and inflammation scores in the kidney specimen than the control and omentum repair groups (P < 0.05). The omentum repair 2 group had significantly lower median granulation and inflammation scores in the surrounding tissues than the primary repair 2 group (P < 0.05). The completion score for the healing process in the kidney specimen was significantly higher in the omentum repair groups than in the primary repair groups (P < 0.05). The omentum repair 2 group had significantly lower median granulation and inflammation scores in the surrounding tissues than the primary repair 2 group (P < 0.05). Granulation degree in the kidney specimen was strongly and positively correlated with the inflammation degree (r = 0.824, P < 0.001) and foreign body reaction in the kidney specimen (r = 0.872, P < 0.001) and a strong and negative correlation with the healing process completion score in the kidney (r = - 0.627, P = 0.001). Inflammation degree in the kidney specimen was strongly and positively correlated with the foreign body reaction in the kidney specimen (r = 0.731, P = 0.001) and strongly and negatively correlated with the healing process completion score in the kidney specimen (r = - 0.608, P = 0.002). CONCLUSION Autologous omentum tissue for kidney injury repair attenuated inflammation and granulation. Additionally, the use of omental tissue to facilitate healing of kidney injury may theoretically lead to a more effective healing process and reduced fibrosis and tissue and function loss.
Collapse
Affiliation(s)
- Tayfun Bilgiç
- Acıbadem Kadıkoy Hospital of General Surgery, Istanbul, 34718 Turkey
| | - Ümit İnce
- Department of Pathology, Acıbadem Mehmet Ali Aydınlar University, Istanbul, 34684 Turkey
| | - Fehmi Narter
- Department of Urology, Acıbadem Mehmet Ali Aydınlar University, Istanbul, 34684 Turkey
| |
Collapse
|
|
3
|
Teratani T, Kasahara N, Ijichi T, Fujimoto Y, Sakuma Y, Sata N, Kitayama J. Activation of whole body by high levels of polyamine intake in rats. Amino Acids 2021; 53:1695-1703. [PMID: 34654958 PMCID: PMC8592999 DOI: 10.1007/s00726-021-03079-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Accepted: 09/17/2021] [Indexed: 11/05/2022]
Abstract
Polyamines are important to the survival and activation of organs and tissues via a homeostatic cell-metabolic process, and the polyamine content in cytoplasm decreases with aging. Decreases in cellular polyamine have been known to augment mutagenesis and cell death. Thus, supplementary polyamine in food is important to the prevention of aging. Here we show the anti-aging effects of oral intake of polyamine using luciferase-transgenic rats. Healthy rats, 10–12 weeks old, were given foods containing 0.01% and 0.1% (w/w) of polyamine, as compared a control food without polyamine, for 4 weeks. Using a bioimaging system, the photon intensities seen in the whole bodies and livers of rats consuming 0.1% of polyamine in food were stronger than those in rats consuming 0.01% and 0% of polyamine. However, there were no differences between groups in other characteristics, such as liver damage and body weight. In conclusion, we found that polyamine intake can activate cells throughout the whole body, providing an anti-aging effect.
Collapse
Affiliation(s)
- Takumi Teratani
- Division of Translational Research, Jichi Medical University, 3311-1, Yakushiji, Shimotsukeshi, Tochigi, 329-0498, Japan. .,Department of Surgery, Jichi Medical University, 3311-1, Yakushiji, Shimotsukeshi, Tochigi, 329-0498, Japan.
| | - Naoya Kasahara
- Department of Surgery, Jichi Medical University, 3311-1, Yakushiji, Shimotsukeshi, Tochigi, 329-0498, Japan
| | - Tetsuo Ijichi
- Division of Translational Research, Jichi Medical University, 3311-1, Yakushiji, Shimotsukeshi, Tochigi, 329-0498, Japan
| | - Yasuhiro Fujimoto
- Department of Surgery, Hyogo College of Medicine, 1-3-6 Minatojima, Chuo-ku, Kobeshi, Hyogo, 663-8501, Japan
| | - Yasunaru Sakuma
- Department of Surgery, Jichi Medical University, 3311-1, Yakushiji, Shimotsukeshi, Tochigi, 329-0498, Japan
| | - Naohiro Sata
- Department of Surgery, Jichi Medical University, 3311-1, Yakushiji, Shimotsukeshi, Tochigi, 329-0498, Japan
| | - Joji Kitayama
- Division of Translational Research, Jichi Medical University, 3311-1, Yakushiji, Shimotsukeshi, Tochigi, 329-0498, Japan.,Department of Surgery, Jichi Medical University, 3311-1, Yakushiji, Shimotsukeshi, Tochigi, 329-0498, Japan
| |
Collapse
|
|
4
|
Storti G, Favi E, Albanesi F, Kim BS, Cervelli V. Adipose-Derived Stem/Stromal Cells in Kidney Transplantation: Status Quo and Future Perspectives. Int J Mol Sci 2021; 22:11188. [PMID: 34681848 PMCID: PMC8538841 DOI: 10.3390/ijms222011188] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 10/11/2021] [Accepted: 10/14/2021] [Indexed: 02/07/2023] Open
Abstract
Kidney transplantation (KT) is the gold standard treatment of end-stage renal disease. Despite progressive advances in organ preservation, surgical technique, intensive care, and immunosuppression, long-term allograft survival has not significantly improved. Among the many peri-operative complications that can jeopardize transplant outcomes, ischemia-reperfusion injury (IRI) deserves special consideration as it is associated with delayed graft function, acute rejection, and premature transplant loss. Over the years, several strategies have been proposed to mitigate the impact of IRI and favor tolerance, with rather disappointing results. There is mounting evidence that adipose stem/stromal cells (ASCs) possess specific characteristics that could help prevent, reduce, or reverse IRI. Immunomodulating and tolerogenic properties have also been suggested, thus leading to the development of ASC-based prophylactic and therapeutic strategies in pre-clinical and clinical models of renal IRI and allograft rejection. ASCs are copious, easy to harvest, and readily expandable in culture. Furthermore, ASCs can secrete extracellular vesicles (EV) which may act as powerful mediators of tissue repair and tolerance. In the present review, we discuss the current knowledge on the mechanisms of action and therapeutic opportunities offered by ASCs and ASC-derived EVs in the KT setting. Most relevant pre-clinical and clinical studies as well as actual limitations and future perspective are highlighted.
Collapse
Affiliation(s)
- Gabriele Storti
- Plastic and Reconstructive Surgery, Department of Surgical Sciences, Tor Vergata University, 00133 Rome, Italy; (G.S.); (V.C.)
| | - Evaldo Favi
- Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy
- Kidney Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20135 Milan, Italy;
| | - Francesca Albanesi
- Kidney Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20135 Milan, Italy;
| | - Bong-Sung Kim
- Division of Plastic Surgery and Hand Surgery, University Hospital Zurich, 8091 Zurich, Switzerland;
| | - Valerio Cervelli
- Plastic and Reconstructive Surgery, Department of Surgical Sciences, Tor Vergata University, 00133 Rome, Italy; (G.S.); (V.C.)
| |
Collapse
|
|
5
|
Liu Y, Su YY, Yang Q, Zhou T. Stem cells in the treatment of renal fibrosis: a review of preclinical and clinical studies of renal fibrosis pathogenesis. Stem Cell Res Ther 2021; 12:333. [PMID: 34112221 PMCID: PMC8194041 DOI: 10.1186/s13287-021-02391-w] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Accepted: 05/14/2021] [Indexed: 02/05/2023] Open
Abstract
Renal fibrosis commonly leads to glomerulosclerosis and renal interstitial fibrosis and the main pathological basis involves tubular atrophy and the abnormal increase and excessive deposition of extracellular matrix (ECM). Renal fibrosis can progress to chronic kidney disease. Stem cells have multilineage differentiation potential under appropriate conditions and are easy to obtain. At present, there have been some studies showing that stem cells can alleviate the accumulation of ECM and renal fibrosis. However, the sources of stem cells and the types of renal fibrosis or renal fibrosis models used in these studies have differed. In this review, we summarize the pathogenesis (including signaling pathways) of renal fibrosis, and the effect of stem cell therapy on renal fibrosis as described in preclinical and clinical studies. We found that stem cells from various sources have certain effects on improving renal function and alleviating renal fibrosis. However, additional clinical studies should be conducted to confirm this conclusion in the future.
Collapse
Affiliation(s)
- Yiping Liu
- Department of Nephrology, the Second Affiliated Hospital of Shantou University Medical College, No. 69 Dongsha Road, Shantou, 515041, China
| | - Yan-Yan Su
- Department of Nephrology, Huadu District People's Hospital of Guangzhou, Southern Medical University, Guangzhou, China
| | - Qian Yang
- Department of Nephrology, the Second Affiliated Hospital of Shantou University Medical College, No. 69 Dongsha Road, Shantou, 515041, China
| | - Tianbiao Zhou
- Department of Nephrology, the Second Affiliated Hospital of Shantou University Medical College, No. 69 Dongsha Road, Shantou, 515041, China.
| |
Collapse
|
|
6
|
Thompson ER, Connelly C, Ali S, Sheerin NS, Wilson CH. Cell therapy during machine perfusion. Transpl Int 2020; 34:49-58. [PMID: 33131097 DOI: 10.1111/tri.13780] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Revised: 06/03/2020] [Accepted: 10/28/2020] [Indexed: 12/12/2022]
Abstract
There has been increasing use of organs from extended criteria or donation after circulatory death donors to meet the demands of the transplant waiting list. Over the past decade, there has been considerable progress in technologies to preserve organs prior to transplantation to improve the function of these marginal organs. This has led to the development of normothermic machine perfusion, whereby an organ is perfused with warmed, oxygenated blood and nutrients to resume normal physiological function in an isolated ex-vivo platform. With this advance in preservation comes significant opportunities to recondition, repair and regenerate organs prior to transplantation using cellular therapies. This review aims to discuss the possibilities of machine perfusion technology; highlighting the potential for organ-directed reconditioning and the future avenues for investigation in this field.
Collapse
Affiliation(s)
- Emily R Thompson
- Translational & Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Chloe Connelly
- Translational & Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Simi Ali
- Translational & Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Neil S Sheerin
- Translational & Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Colin H Wilson
- Translational & Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
| |
Collapse
|
|
7
|
Oliva J. Therapeutic Properties of Mesenchymal Stem Cell on Organ Ischemia-Reperfusion Injury. Int J Mol Sci 2019; 20:ijms20215511. [PMID: 31694240 PMCID: PMC6862572 DOI: 10.3390/ijms20215511] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2019] [Revised: 10/29/2019] [Accepted: 11/02/2019] [Indexed: 12/13/2022] Open
Abstract
The shortage of donor organs is a major global concern. Organ failure requires the transplantation of functional organs. Donor’s organs are preserved for variable periods of warm and cold ischemia time, which requires placing them into a preservation device. Ischemia and reperfusion damage the organs, due to the lack of oxygen during the ischemia step, as well as the oxidative stress during the reperfusion step. Different methodologies are developed to prevent or to diminish the level of injuries. Preservation solutions were first developed to maximize cold static preservation, which includes the addition of several chemical compounds. The next chapter of organ preservation comes with the perfusion machine, where mechanical devices provide continuous flow and oxygenation ex vivo to the organs being preserved. In the addition of inhibitors of mitogen-activated protein kinase and inhibitors of the proteasome, mesenchymal stem cells began being used 13 years ago to prevent or diminish the organ’s injuries. Mesenchymal stem cells (e.g., bone marrow stem cells, adipose derived stem cells and umbilical cord stem cells) have proven to be powerful tools in repairing damaged organs. This review will focus upon the use of some bone marrow stem cells, adipose-derived stem cells and umbilical cord stem cells on preventing or decreasing the injuries due to ischemia-reperfusion.
Collapse
Affiliation(s)
- Joan Oliva
- Emmaus Medical, Inc., 21250 Hawthorne Blvd, Suite 800, Torrance, CA 90503, USA
| |
Collapse
|
|
8
|
Kobayashi E, Sano M. Organ preservation solution containing dissolved hydrogen gas from a hydrogen-absorbing alloy canister improves function of transplanted ischemic kidneys in miniature pigs. PLoS One 2019; 14:e0222863. [PMID: 31574107 PMCID: PMC6772054 DOI: 10.1371/journal.pone.0222863] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2019] [Accepted: 09/09/2019] [Indexed: 12/11/2022] Open
Abstract
Various methods have been devised to dissolve hydrogen gas in organ preservation solutions, including use of a hydrogen gas cylinder, electrolysis, or a hydrogen-generating agent. However, these methods require considerable time and effort for preparation. We investigated a practical technique for rapidly dissolving hydrogen gas in organ preservation solutions by using a canister containing hydrogen-absorbing alloy. The efficacy of hydrogen-containing organ preservation solution created by this method was tested in a miniature pig model of kidney transplantation from donors with circulatory arrest. The time required for dissolution of hydrogen gas was only 2–3 minutes. When hydrogen gas was infused into a bag containing cold ETK organ preservation solution at a pressure of 0.06 MPa and the bag was subsequently opened to the air, the dissolved hydrogen concentration remained at 1.0 mg/L or more for 4 hours. After warm ischemic injury was induced by circulatory arrest for 30 minutes, donor kidneys were harvested and perfused for 5 minutes with hydrogen-containing cold ETK solution or hydrogen-free cold ETK solution. The perfusion rate was faster from the initial stage with hydrogen-containing cold ETK solution than with hydrogen-free ETK solution. After storage of the kidney in hydrogen-free preservation solution for 1 hour before transplantation, no urine production was observed and blood flow was not detected in the transplanted kidney at sacrifice on postoperative day 6. In contrast, after storage in hydrogen-containing preservation solution for either 1 or 4 hours, urine was detected in the bladder and blood flow was confirmed in the transplanted kidney. This method of dissolving hydrogen gas in organ preservation solution is a practical technique for potentially converting damaged organs to transplantable organs that can be used safely in any clinical setting where organs are removed from donors.
Collapse
Affiliation(s)
- Eiji Kobayashi
- Department of Cardiology, Keio University School of Medicine, Tokyo, Japan
- Department of Organ Fabrication, Keio University School of Medicine, Tokyo, Japan
- Center for Molecular Hydrogen Medicine, Keio University, Tokyo, Japan
| | - Motoaki Sano
- Department of Cardiology, Keio University School of Medicine, Tokyo, Japan
- Center for Molecular Hydrogen Medicine, Keio University, Tokyo, Japan
- * E-mail:
| |
Collapse
|
|
9
|
Sierra-Parraga JM, Munk A, Andersen C, Lohmann S, Moers C, Baan CC, Ploeg RJ, Pool M, Keller AK, Møller BK, Leuvenink H, Hoogduijn MJ, Jespersen B, Eijken M. Mesenchymal Stromal Cells Are Retained in the Porcine Renal Cortex Independently of Their Metabolic State After Renal Intra-Arterial Infusion. Stem Cells Dev 2019; 28:1224-1235. [PMID: 31280676 DOI: 10.1089/scd.2019.0105] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
The regenerative capacities of mesenchymal stromal cells (MSCs) make them suitable for renal regenerative therapy. The most common delivery route of MSC is through intravenous infusion, which is associated with off-target distribution. Renal intra-arterial delivery offers a targeted therapy, but limited knowledge is available regarding the fate of MSCs delivered through this route. Therefore, we studied the efficiency and tissue distribution of MSCs after renal intra-arterial delivery to a porcine renal ischemia-reperfusion model. MSCs were isolated from adipose tissue of healthy male pigs, fluorescently labeled and infused into the renal artery of female pigs. Flow cytometry allowed MSC detection and quantification in tissue and blood. In addition, quantitative polymerase chain reaction was used to trace MSCs by their Y-chromosome. During infusion, a minor number of MSCs left the kidney through the renal vein, and no MSCs were identified in arterial blood. Ischemic and healthy renal tissues were analyzed 30 min and 8 h after infusion, and 1-4 × 104 MSCs per gram of tissue were detected, predominantly, in the renal cortex, with a viability >70%. Confocal microscopy demonstrated mainly glomerular localization of MSCs, but they were also observed in the capillary network around tubuli. The infusion of heat-inactivated (HI) MSCs, which are metabolically inactive, through the renal artery showed that HI-MSCs were distributed in the kidney in a similar manner to regular MSCs, suggesting a passive retention mechanism. Long-term MSC survival was analyzed by Y-chromosome tracing, and demonstrated that a low percentage of the infused MSCs were present in the kidney 14 days after administration, while HI-MSCs were completely undetectable. In conclusion, renal intra-arterial MSC infusion limited off-target engraftment, leading to efficient MSC delivery to the kidney, most of them being cleared within 14 days. MSC retention was independent of the metabolic state of MSC, indicating a passive mechanism.
Collapse
Affiliation(s)
- Jesus M Sierra-Parraga
- Nephrology and Transplantation, Internal Medicine Department, University Medical Center Rotterdam, Erasmus MC, Rotterdam, the Netherlands.,Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark
| | - Anders Munk
- Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | | | - Stine Lohmann
- Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark.,Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Cyril Moers
- Department of Surgery-Organ Donation and Transplantation, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Carla C Baan
- Nephrology and Transplantation, Internal Medicine Department, University Medical Center Rotterdam, Erasmus MC, Rotterdam, the Netherlands
| | - Rutger J Ploeg
- Nuffield Department of Surgical Sciences and Oxford Biomedical Research Centre, University of Oxford, Oxford, United Kingdom
| | - Merel Pool
- Department of Surgery-Organ Donation and Transplantation, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Anna K Keller
- Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark
| | - Bjarne K Møller
- Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark
| | - Henri Leuvenink
- Department of Surgery-Organ Donation and Transplantation, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Martin J Hoogduijn
- Nephrology and Transplantation, Internal Medicine Department, University Medical Center Rotterdam, Erasmus MC, Rotterdam, the Netherlands
| | - Bente Jespersen
- Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Marco Eijken
- Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.,Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark
| |
Collapse
|
|
10
|
Abstract
PURPOSE OF REVIEW Normothermic machine perfusion (NMP) is an emerging technology for liver preservation. Early clinical results demonstrate beneficial effects in reconditioning high-risk grafts. This review discusses the role of normothermic perfusion as a tool to assess graft viability and as a platform for graft intervention and modification. RECENT FINDINGS The potential benefits of NMP extend far beyond organ reconditioning. Recent pilot studies have identified clinically relevant viability criteria, which now require validation in large randomized control trials prior to implementation. Furthermore, preclinical studies demonstrate tremendous potential for NMP as a method to extend the preservation period, thus improving transplant logistics as well as serve as a platform for graft-targeted interventions to optimize the preservation period. SUMMARY NMP is a multifunctional tool with potential to transform liver preservation and the field of transplantation. Large clinical trials are necessary to optimize perfusion protocols, clarify indications for NMP therapy and justify use as the standard preservation modality.
Collapse
|
|
11
|
Mesenchymal Stem Cells-Potential Applications in Kidney Diseases. Int J Mol Sci 2019; 20:ijms20102462. [PMID: 31109047 PMCID: PMC6566143 DOI: 10.3390/ijms20102462] [Citation(s) in RCA: 55] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2019] [Revised: 05/16/2019] [Accepted: 05/16/2019] [Indexed: 12/12/2022] Open
Abstract
Mesenchymal stem cells constitute a pool of cells present throughout the lifetime in numerous niches, characteristic of unlimited replication potential and the ability to differentiate into mature cells of mesodermal tissues in vitro. The therapeutic potential of these cells is, however, primarily associated with their capabilities of inhibiting inflammation and initiating tissue regeneration. Owing to these properties, mesenchymal stem cells (derived from the bone marrow, subcutaneous adipose tissue, and increasingly urine) are the subject of research in the settings of kidney diseases in which inflammation plays the key role. The most advanced studies, with the first clinical trials, apply to ischemic acute kidney injury, renal transplantation, lupus and diabetic nephropathies, in which beneficial clinical effects of cells themselves, as well as their culture medium, were observed. The study findings imply that mesenchymal stem cells act predominantly through secreted factors, including, above all, microRNAs contained within extracellular vesicles. Research over the coming years will focus on this secretome as a possible therapeutic agent void of the potential carcinogenicity of the cells.
Collapse
|
|
12
|
Xie LB, Chen X, Chen B, Wang XD, Jiang R, Lu YP. Protective effect of bone marrow mesenchymal stem cells modified with klotho on renal ischemia-reperfusion injury. Ren Fail 2019; 41:175-182. [PMID: 30942135 PMCID: PMC6450585 DOI: 10.1080/0886022x.2019.1588131] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Objective: To detect the combination protective effect of bone marrow mesenchymal stem cells (BMSCs) and Klotho gene on the renal ischemia-reperfusion injury (RIRI). Methods: BMSCs isolated from rats were transfected with Klotho gene to form BMSCKl. We injected BMSCKl to allogenic rat RIRI model. After 24 h and 72 h, we detected the serum creatinine (SCr), malondialdehyde (MDA), and superoxide dismutase (SOD) in renal tissue, Hematoxylin-eosin (HE) staining, and TUNEL of renal pathology. The expression of FoxO1 and p-FoxO1 in post-hypoxia tubular epithelial cells of normal rat kidney (NRK-52E) were detected by Western blot after cocultured with BMSCKl. Results: Comparing with BMSCCon group, Rats in BMSCKl group had lower SCr and MDA but higher SOD. Both HE and TUNEL score of renal tissue in BMSCKl group were lower than that of BMSCCon group. Western blot indicated that FoxO1 was upregulated, while p-FoxO1 was downregulated in post-hypoxia NRK-52E cells. Conclusions: BMSCs transfected with Klotho gene can further ameliorate RIRI. The possible mechanism may be attributed to the upregulation of SOD in NRK-52E caused by Klotho-FoxO1 axis.
Collapse
Affiliation(s)
- Li-Bo Xie
- a Department of Urology , The Affiliated Hospital of Southwest Medical University , Luzhou , China
| | - Xi Chen
- b School of Biology Science , East China Normal University , Shanghai , China
| | - Bo Chen
- c Department of Human Anatomy , Southwest Medical University , Luzhou , China
| | - Xian-Ding Wang
- d Department of Urology , The Institution of Urology, West China Hospital, Sichuan University , Chengdu , China
| | - Rui Jiang
- a Department of Urology , The Affiliated Hospital of Southwest Medical University , Luzhou , China
| | - Yi-Ping Lu
- d Department of Urology , The Institution of Urology, West China Hospital, Sichuan University , Chengdu , China
| |
Collapse
|
|
13
|
Zhuang Q, Ma R, Yin Y, Lan T, Yu M, Ming Y. Mesenchymal Stem Cells in Renal Fibrosis: The Flame of Cytotherapy. Stem Cells Int 2019; 2019:8387350. [PMID: 30766607 PMCID: PMC6350586 DOI: 10.1155/2019/8387350] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2018] [Accepted: 11/27/2018] [Indexed: 12/24/2022] Open
Abstract
Renal fibrosis, as the fundamental pathological process of chronic kidney disease (CKD), is a pathologic extension of the normal wound healing process characterized by endothelium injury, myofibroblast activation, macrophage migration, inflammatory signaling stimulation, matrix deposition, and remodelling. Yet, the current method of treating renal fibrosis is fairly limited, including angiotensin-converting enzyme inhibition, angiotensin receptor blockade, optimal blood pressure control, and sodium bicarbonate for metabolic acidosis. MSCs are pluripotent adult stem cells that can differentiate into various types of tissue lineages, such as the cartilage (chondrocytes), bone (osteoblasts), fat (adipocytes), and muscle (myocytes). Because of their many advantages like ubiquitous sources, convenient procurement and collection, low immunogenicity, and low adverse effects, with their special identification markers, mesenchymal stem MSC-based therapy is getting more and more attention. Based on the mechanism of renal fibrosis, MSCs mostly participate throughout the renal fibrotic process. According to the latest and overall literature reviews, we aim to elucidate the antifibrotic mechanisms and effects of diverse sources of MSCs on renal fibrosis, assess their efficacy and safety in preliminarily clinical application, answer the controversial questions, and provide novel ideas into the MSC cellular therapy of renal fibrosis.
Collapse
Affiliation(s)
- Quan Zhuang
- Transplantation Center of The 3rd Xiangya Hospital, Central South University, Changsha, Hunan 410013, China
- Research Center of National Health Ministry on Transplantation Medicine, Changsha, Hunan 410013, China
| | - Ruoyu Ma
- Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, China
| | - Yanshuang Yin
- Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, China
| | - Tianhao Lan
- Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, China
| | - Meng Yu
- Transplantation Center of The 3rd Xiangya Hospital, Central South University, Changsha, Hunan 410013, China
- Research Center of National Health Ministry on Transplantation Medicine, Changsha, Hunan 410013, China
| | - Yingzi Ming
- Transplantation Center of The 3rd Xiangya Hospital, Central South University, Changsha, Hunan 410013, China
- Research Center of National Health Ministry on Transplantation Medicine, Changsha, Hunan 410013, China
| |
Collapse
|
|
14
|
Torres Crigna A, Daniele C, Gamez C, Medina Balbuena S, Pastene DO, Nardozi D, Brenna C, Yard B, Gretz N, Bieback K. Stem/Stromal Cells for Treatment of Kidney Injuries With Focus on Preclinical Models. Front Med (Lausanne) 2018; 5:179. [PMID: 29963554 PMCID: PMC6013716 DOI: 10.3389/fmed.2018.00179] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2018] [Accepted: 05/24/2018] [Indexed: 12/18/2022] Open
Abstract
Within the last years, the use of stem cells (embryonic, induced pluripotent stem cells, or hematopoietic stem cells), Progenitor cells (e.g., endothelial progenitor cells), and most intensely mesenchymal stromal cells (MSC) has emerged as a promising cell-based therapy for several diseases including nephropathy. For patients with end-stage renal disease (ESRD), dialysis or finally organ transplantation are the only therapeutic modalities available. Since ESRD is associated with a high healthcare expenditure, MSC therapy represents an innovative approach. In a variety of preclinical and clinical studies, MSC have shown to exert renoprotective properties, mediated mainly by paracrine effects, immunomodulation, regulation of inflammation, secretion of several trophic factors, and possibly differentiation to renal precursors. However, studies are highly diverse; thus, knowledge is still limited regarding the exact mode of action, source of MSC in comparison to other stem cell types, administration route and dose, tracking of cells and documentation of therapeutic efficacy by new imaging techniques and tissue visualization. The aim of this review is to provide a summary of published studies of stem cell therapy in acute and chronic kidney injury, diabetic nephropathy, polycystic kidney disease, and kidney transplantation. Preclinical studies with allogeneic or xenogeneic cell therapy were first addressed, followed by a summary of clinical trials carried out with autologous or allogeneic hMSC. Studies were analyzed with respect to source of cell type, mechanism of action etc.
Collapse
Affiliation(s)
- Adriana Torres Crigna
- Medical Faculty Mannheim, Institute of Transfusion Medicine and Immunology, University of Heidelberg, German Red Cross Blood Service Baden-Württemberg-Hessen, Mannheim, Germany
| | - Cristina Daniele
- Medical Faculty Mannheim, Medical Research Centre, University of Heidelberg, Mannheim, Germany
| | - Carolina Gamez
- Department for Experimental Orthopaedics and Trauma Surgery, Medical Faculty Mannheim, Orthopaedic and Trauma Surgery Centre (OUZ), Heidelberg University, Mannheim, Germany
| | - Sara Medina Balbuena
- Department of Medicine (Nephrology/Endrocrinology/Rheumathology), University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany
| | - Diego O. Pastene
- Department of Medicine (Nephrology/Endrocrinology/Rheumathology), University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany
| | - Daniela Nardozi
- Medical Faculty Mannheim, Medical Research Centre, University of Heidelberg, Mannheim, Germany
| | - Cinzia Brenna
- Medical Faculty Mannheim, Medical Research Centre, University of Heidelberg, Mannheim, Germany
| | - Benito Yard
- Department of Medicine (Nephrology/Endrocrinology/Rheumathology), University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany
| | - Norbert Gretz
- Medical Faculty Mannheim, Medical Research Centre, University of Heidelberg, Mannheim, Germany
| | - Karen Bieback
- Medical Faculty Mannheim, Institute of Transfusion Medicine and Immunology, University of Heidelberg, German Red Cross Blood Service Baden-Württemberg-Hessen, Mannheim, Germany
| |
Collapse
|
|
15
|
Jing H, He X, Zheng J. Exosomes and regenerative medicine: state of the art and perspectives. Transl Res 2018; 196:1-16. [PMID: 29432720 DOI: 10.1016/j.trsl.2018.01.005] [Citation(s) in RCA: 102] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2017] [Revised: 01/18/2018] [Accepted: 01/18/2018] [Indexed: 12/19/2022]
Abstract
Exosomes have attracted the attention of the scientific community in recent years due to their widespread distribution, their possible functions as biomarkers of disease, and their great potential to be applied as therapeutic agents. Exosomes carry proteins and nucleic acids that can facilitate their uptake by distant target cells through endocytosis, such that exosomes could be targeted to a specific cell or cells to enhance or interfere with specific biological processes. This review will mainly focus on their roles in tissue repair and regenerative processes. Exosomal engineering and their potential applications in tissue regeneration are also reviewed here as an outlook for future research.
Collapse
Affiliation(s)
- Hui Jing
- Department of Cardiothoracic Surgery, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaomin He
- Department of Cardiothoracic Surgery, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Jinghao Zheng
- Department of Cardiothoracic Surgery, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| |
Collapse
|
|
16
|
Mullins LJ, Conway BR, Menzies RI, Denby L, Mullins JJ. Renal disease pathophysiology and treatment: contributions from the rat. Dis Model Mech 2017; 9:1419-1433. [PMID: 27935823 PMCID: PMC5200898 DOI: 10.1242/dmm.027276] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
The rat has classically been the species of choice for pharmacological studies and disease modeling, providing a source of high-quality physiological data on cardiovascular and renal pathophysiology over many decades. Recent developments in genome engineering now allow us to capitalize on the wealth of knowledge acquired over the last century. Here, we review rat models of hypertension, diabetic nephropathy, and acute and chronic kidney disease. These models have made important contributions to our understanding of renal diseases and have revealed key genes, such as Ace and P2rx7, involved in renal pathogenic processes. By targeting these genes of interest, researchers are gaining a better understanding of the etiology of renal pathologies, with the promised potential of slowing disease progression or even reversing the damage caused. Some, but not all, of these target genes have proved to be of clinical relevance. However, it is now possible to generate more sophisticated and appropriate disease models in the rat, which can recapitulate key aspects of human renal pathology. These advances will ultimately be used to identify new treatments and therapeutic targets of much greater clinical relevance. Summary: This Review highlights the key role that the rat continues to play in improving our understanding of the etiologies of renal pathologies, and how these insights have opened up new therapeutic avenues.
Collapse
Affiliation(s)
- Linda J Mullins
- University of Edinburgh/British Heart Foundation Centre for Cardiovascular Science, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK
| | - Bryan R Conway
- University of Edinburgh/British Heart Foundation Centre for Cardiovascular Science, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK
| | - Robert I Menzies
- University of Edinburgh/British Heart Foundation Centre for Cardiovascular Science, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK
| | - Laura Denby
- University of Edinburgh/British Heart Foundation Centre for Cardiovascular Science, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK
| | - John J Mullins
- University of Edinburgh/British Heart Foundation Centre for Cardiovascular Science, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK
| |
Collapse
|
|
17
|
Sierra-Parraga JM, Eijken M, Hunter J, Moers C, Leuvenink H, Møller B, Ploeg RJ, Baan CC, Jespersen B, Hoogduijn MJ. Mesenchymal Stromal Cells as Anti-Inflammatory and Regenerative Mediators for Donor Kidneys During Normothermic Machine Perfusion. Stem Cells Dev 2017; 26:1162-1170. [PMID: 28557562 DOI: 10.1089/scd.2017.0030] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
There is great demand for transplant kidneys for the treatment of end-stage kidney disease patients. To expand the donor pool, organs from older and comorbid brain death donors, so-called expanded criteria donors (ECD), as well as donation after circulatory death donors, are considered for transplantation. However, the quality of these organs may be inferior to standard donor organs. A major issue affecting graft function and survival is ischemia/reperfusion injury, which particularly affects kidneys from deceased donors. The development of hypothermic machine perfusion has been introduced in kidney transplantation as a preservation technique and has improved outcomes in ECD and marginal organs compared to static cold storage. Normothermic machine perfusion (NMP) is the most recent evolution of perfusion technology and allows assessment of the donor organ before transplantation. The possibility to control the content of the perfusion fluid offers opportunities for damage control and reparative therapies during machine perfusion. Mesenchymal stromal cells (MSC) have been demonstrated to possess potent regenerative properties via the release of paracrine effectors. The combination of NMP and MSC administration at the same time is a promising procedure in the field of transplantation. Therefore, the MePEP consortium has been created to study this novel modality of treatment in preparation for human trials. MePEP aims to assess the therapeutic effects of MSC administered ex vivo by NMP in the mechanisms of injury and repair in a porcine kidney autotransplantation model.
Collapse
Affiliation(s)
- Jesus Maria Sierra-Parraga
- 1 Department of Internal Medicine, Nephrology and Transplantation, Erasmus MC, University Medical Center , Rotterdam, the Netherlands
| | - Marco Eijken
- 2 Institute of Clinical Medicine, Department of Medicine and Nephrology C, Aarhus University , Aarhus, Denmark
| | - James Hunter
- 3 Nuffield Department of Surgical Sciences, Oxford Biomedical Research Centre, University of Oxford , Oxford, United Kingdom
| | - Cyril Moers
- 4 Department of Surgery-Organ Donation and Transplantation, University of Medical Center Groningen , Groningen, the Netherlands
| | - Henri Leuvenink
- 4 Department of Surgery-Organ Donation and Transplantation, University of Medical Center Groningen , Groningen, the Netherlands
| | - Bjarne Møller
- 5 Department of Clinical Immunology, Aarhus University Hospital , Aarhus, Denmark
| | - Rutger J Ploeg
- 3 Nuffield Department of Surgical Sciences, Oxford Biomedical Research Centre, University of Oxford , Oxford, United Kingdom
| | - Carla C Baan
- 1 Department of Internal Medicine, Nephrology and Transplantation, Erasmus MC, University Medical Center , Rotterdam, the Netherlands
| | - Bente Jespersen
- 6 Department of Renal Medicine, Aarhus University Hospital , Aarhus, Denmark
| | - Martin J Hoogduijn
- 1 Department of Internal Medicine, Nephrology and Transplantation, Erasmus MC, University Medical Center , Rotterdam, the Netherlands
| |
Collapse
|
|
18
|
Karimian N, Yeh H. Opportunities for Therapeutic Intervention During Machine Perfusion. CURRENT TRANSPLANTATION REPORTS 2017; 4:141-148. [PMID: 29109929 PMCID: PMC5669266 DOI: 10.1007/s40472-017-0144-y] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
PURPOSE OF REVIEW There is a vast discrepancy between the number of patients waiting for organ transplantation and the available donor organs. Ex vivo machine perfusion (MP) has emerged in an effort to expand the donor pool, by improving organ preservation, providing diagnostic information, and more recently, acting as a platform for organ improvement. This article reviews the current status of MP with a focus on its role in organ preconditioning and therapeutic interventions prior to transplantation. RECENT FINDINGS MP has allowed longer organ preservation compared to conventional static cold storage and allowed the use of organs that might otherwise have been discarded. Moreover, experimental studies have investigated the role of MP in reducing ischemia reperfusion injury of lungs, kidneys and livers by applying mesenchymal stem cells (MSCs), anti-inflammatory agents, cytotopic anticoagulants, and defatting cocktails. SUMMARY MP has opened a new era in the field of organ transplantation and tissue medication.
Collapse
Affiliation(s)
- Negin Karimian
- Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, USA
- Center for Engineering in Medicine, Harvard Medical School, Boston, USA
| | - Heidi Yeh
- Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, USA
| |
Collapse
|
|
19
|
Abstract
The described research methods explain how you could generate a three-dimensional kidney, based on recent research results. The first method is to fabricate human organs in a pig body. The second is to transplant the so-called "organ bud" into a patient's body for further development. The third method is to regenerate organs by filling cells into the cytoskeleton as a scaffold. Research for the in vitro fabrication of organ buds has been elaborately accelerated. The organ bud transplantation has been confronted with issues of continuity with the original organs, so the development of technology for achieving continuity between a transplanted organ bud and the existing organs is progressing well. The "organ fabrication" methodology, whereby cells are placed into completely decellularized organs, is supported by recent research results using pig organs taking the size of humans into consideration.
Collapse
Affiliation(s)
- Eiji Kobayashi
- Department of Organ Fabrication, Keio University School of Medicine , Tokyo , Japan
| |
Collapse
|
|
20
|
Abstract
PURPOSE OF REVIEW To summarize the history of organ preservation and place into this context the current trends in preservation. RECENT FINDINGS Multiple large retrospective studies have analyzed cold preservation solutions in an attempt to determine superiority with largely negative results. Experimental and some clinical studies have examined machine perfusion of procured grafts, in both hypothermic and normothermic contexts with variable, but promising, results. Lastly, there are experimental efforts to evaluate mesenchymal stem cell therapy on rehabilitation of marginal donor organs. SUMMARY New trends in organ preservation may soon translate into more efficient use of the limited donor pool.
Collapse
|
|
21
|
Bejaoui M, Pantazi E, Folch-Puy E, Baptista PM, García-Gil A, Adam R, Roselló-Catafau J. Emerging concepts in liver graft preservation. World J Gastroenterol 2015; 21:396-407. [PMID: 25593455 PMCID: PMC4292271 DOI: 10.3748/wjg.v21.i2.396] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2014] [Revised: 10/24/2014] [Accepted: 12/08/2014] [Indexed: 02/06/2023] Open
Abstract
The urgent need to expand the donor pool in order to attend to the growing demand for liver transplantation has obliged physicians to consider the use of suboptimal liver grafts and also to redefine the preservation strategies. This review examines the different methods of liver graft preservation, focusing on the latest advances in both static cold storage and machine perfusion (MP). The new strategies for static cold storage are mainly designed to increase the fatty liver graft preservation via the supplementation of commercial organ preservation solutions with additives. In this paper we stress the importance of carrying out effective graft washout after static cold preservation, and present a detailed discussion of the future perspectives for dynamic graft preservation using MP at different temperatures (hypothermia at 4 °C, normothermia at 37 °C and subnormothermia at 20 °C-25 °C). Finally, we highlight some emerging applications of regenerative medicine in liver graft preservation. In conclusion, this review discusses the "state of the art" and future perspectives in static and dynamic liver graft preservation in order to improve graft viability.
Collapse
|