Immunosuppressive Activity of Adipose Tissue-Derived Mesenchymal Stem Cells in a Rat Model of Hind Limb Allotransplantation

Jeong, Seonghee; Yi, Ji; Yoon, Eul Sik

doi:10.1016/j.transproceed.2013.12.069

Cited by 25 publications

(18 citation statements)

References 26 publications

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“…Recent literature evidence reaffirms that an induction regimen or early short-course immunosuppression is probably essential for the success of tolerance strategies [34,35]. Eggenhofer et al reported accelerate rejection and worse outcomes after MSC therapy without concomitant immunosuppression [36].…”

Section: Drug-mesenchymal Stem Cell Interactionsmentioning

confidence: 96%

“…Lee et al reported that in the absence of preconditioning, hASCs achieved only a discrete prolongation of murine allogeneic skin grafts survival injection of conditioned medium prolonged graft survival and reduced inflammatory tissue cytokine levels, suggesting a paracrine mechanism [34]. In another study, repetitive administration of omental rat ASCs over 3 days without adjunct immunosuppression delayed skin graft rejection without long-term tolerance, despite increased T reg levels in skin specimens [35]. Similarly, Larocca et al found that allogeneic ASCs can prolong skin graft survival and recruit T regs into draining lymph nodes.…”

Section: Drug-mesenchymal Stem Cell Interactionsmentioning

confidence: 99%

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Premise and promise of mesenchymal stem cell-based therapies in clinical vascularized composite allotransplantation

Schweizer

Gorantla

Plock

2015

Current Opinion in Organ Transplantation

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PURPOSE OF REVIEW Over the past decade, clinical vascularized composite allotransplantation (VCA) has enabled functional and quality of life restoration in a wide range of indications secondary to devastating tissue loss. However, the spectre of toxicity and long-term complications of chronic immunosuppression has curtailed the momentum of VCA. This study summarizes the literature evidence behind successful mesenchymal stem cell (MSC)-based cell therapies highlighting their multipronged immunomodulatory, restorative and regenerative characteristics with special emphasis towards VCA applications. RECENT FINDINGS Experimental and clinical studies in solid organs and VCA have confirmed that MSCs facilitate immunosuppression-free allograft survival or tolerance, stimulate peripheral nerve regeneration, attenuate ischaemia-reperfusion injury, and improve tissue healing after surgery. It has been hypothesized that MSC-induced long-term operational tolerance in experimental VCA is mediated by induction of mixed donor-specific chimerism and regulatory T-cell mechanisms. All these characteristics of MSCs could thus help expand the scope and clinical feasibility of VCA. SUMMARY Cellular therapies, especially those focusing on MSCs, are emerging in solid organ transplantation including VCA. Although some clinical trials have begun to assess the effects of MSCs in solid organ transplantation, much scientific domain remains uncharted, especially for VCA. Purpose of review Over the past decade, clinical vascularized composite allotransplantation (VCA) has enabled functional and quality of life restoration in a wide range of indications secondary to devastating tissue loss. However, the spectre of toxicity and long-term complications of chronic immunosuppression has curtailed the momentum of VCA. This study summarizes the literature evidence behind successful mesenchymal stem cell (MSC)-based cell therapies highlighting their multipronged immunomodulatory, restorative and regenerative characteristics with special emphasis towards VCA applications. Recent findingsExperimental and clinical studies in solid organs and VCA have confirmed that MSCs facilitate immunosuppression-free allograft survival or tolerance, stimulate peripheral nerve regeneration, attenuate ischaemia-reperfusion injury, and improve tissue healing after surgery. It has been hypothesized that MSCinduced long-term operational tolerance in experimental VCA is mediated by induction of mixed donorspecific chimerism and regulatory T-cell mechanisms. All these characteristics of MSCs could thus help expand the scope and clinical feasibility of VCA. SummaryCellular therapies, especially those focusing on MSCs, are emerging in solid organ transplantation including VCA. Although some clinical trials have begun to assess the effects of MSCs in solid organ transplantation, much scientific domain remains uncharted, especially for VCA.

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Section: Drug-mesenchymal Stem Cell Interactionsmentioning

confidence: 96%

Section: Drug-mesenchymal Stem Cell Interactionsmentioning

confidence: 99%

Premise and promise of mesenchymal stem cell-based therapies in clinical vascularized composite allotransplantation

Schweizer

Gorantla

Plock

2015

Current Opinion in Organ Transplantation

View full text Add to dashboard Cite

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“…Table 1 includes all studies known to the authors that have assessed outcomes of MSC immunomodulatory therapy in the setting of animal VCA or skin allotransplantation [23–31, 33–37, 62]. Since skin is the most antigenic component of VCA and it has been reported to be the first tissue to show signs of rejection in human hand transplantations, skin allograft trials are a useful proxy for outcomes in a VCA setting [31, 32, 63].…”

Section: Preclinical In Vivo Studies Of the Immunosuppressive Effementioning

confidence: 99%

“…Likewise, quantification of the populations of T regs in allotransplant tissue and the circulation (Table 3) shows increased T reg levels in allotransplant tissue, typically in greater number at the dermal-epidermal junction, in all studies that used this approach [27–30, 33] except one [31]. Comparing T reg levels in the serum of animals treated with combined MSC and pharmacological immunosuppression in those with VCA tolerance versus those with VCA rejection shows a significantly greater number of peripheral T regs in immunotolerant animals [34, 35].…”

Section: Monitoring Of Rejection and Local Immunomodulationmentioning

confidence: 99%

Immunomodulatory Role of Mesenchymal Stem Cell Therapy in Vascularized Composite Allotransplantation

Heyes

Iarocci

Tchoukalova

et al. 2016

Journal of Transplantation

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This review aims to summarize contemporary evidence of the in vitro and in vivo immunomodulatory effects of mesenchymal stem cells (MSCs) in promoting vascularized composite allotransplant (VCA) tolerance. An extensive literature review was performed to identify pertinent articles of merit. Prospective preclinical trials in mammal subjects receiving VCA (or skin allograft) with administration of MSCs were reviewed. Prospective clinical trials with intravascular delivery of MSCs in human populations undergoing solid organ transplant were also identified and reviewed. Sixteen preclinical studies are included. Eleven studies compared MSC monotherapy to no therapy; of these, ten reported improved graft survival, which was statistically significantly prolonged in eight. Eight studies analyzed allograft survival with MSC therapy as an adjunct to proven immunosuppressive regimens. In these studies, daily immunosuppression was transiently delivered and then stopped. In all studies, treatment-free graft survival was statistically significantly prolonged in animals that received MSC therapy. MSCs have been safely administered clinically and their use in renal transplant clinical trials provides evidence that they improve allograft transplant tolerance in clinical practice. There is potential for MSC induction therapy to overcome many of the obstacles to widespread VCA in clinical practice. Preclinical studies are needed before MSC-induced VCA tolerance becomes a clinical reality.

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“…It is not consensual if allogeneic delivery of MSCs would lead to immune rejection. Actually, many findings with somatic stem cells showed that they possess immunossupressive action, not being rejected by the host organism [99][100][101][102] . If lack of immune rejection becomes confirmed for allogeneic somatic stem cell transplants, this would certainly represent the preferred option, making it possible that cultured cells are readily available for the patients.…”

Section: Stem Cell Types and Clinical Applications: An Everemerging Smentioning

confidence: 99%

Stem cell therapy in intracerebral hemorrhage rat model

Cordeiro

Horn

2015

WJSC

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Intracerebral hemorrhage (ICH) is a very complex pathology, with many different not fully elucidated etiologies and prognostics. It is the most severe subtype of stroke, with high mortality and morbidity rates. Unfortunately, despite the numerous promising preclinical assays including neuroprotective, anti-hypertensive, and anti-inflammatory drugs, to this moment only symptomatic treatments are available, motivating the search for new alternatives. In this context, stem cell therapy emerged as a promising tool. However, more than a decade has passed, and there is still much to be learned not only about stem cells, but also about ICH itself, and how these two pieces come together. To date, rats have been the most widely used animal model in this research field, and there is much more to be learned from and about them. In this review, we first summarize ICH epidemiology, risk factors, and pathophysiology. We then present different methods utilized to induce ICH in rats, and examine how accurately they represent the human disease. Next, we discuss the different types of stem cells used in previous ICH studies, also taking into account the tested transplantation sites. Finally, we summarize what has been achieved in assays with stem cells in rat models of ICH, and point out some relevant issues where attention must be given in future efforts. Core tip: In this review, we first summarize intracerebral hemorrhage (ICH) epidemiology, risk factors, and pathophysiology. We then present different methods utilized to induce ICH in rats, and examine how accurately they represent the human disease. Next, we discuss the different types of stem cells used in previous ICH studies, also taking into account the tested transplantation sites. Finally, we summarize what has been achieved in assays with stem cells in rat models of ICH, and point out some relevant issues where attention must be given in future efforts.Cordeiro MF, Horn AP. Stem cell therapy in intracerebral hemorrhage rat model. World J Stem Cells 2015; 7(3): 618-629

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Immunosuppressive Activity of Adipose Tissue-Derived Mesenchymal Stem Cells in a Rat Model of Hind Limb Allotransplantation

Cited by 25 publications

References 26 publications

Premise and promise of mesenchymal stem cell-based therapies in clinical vascularized composite allotransplantation

Premise and promise of mesenchymal stem cell-based therapies in clinical vascularized composite allotransplantation

Immunomodulatory Role of Mesenchymal Stem Cell Therapy in Vascularized Composite Allotransplantation

Stem cell therapy in intracerebral hemorrhage rat model

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