Cell therapy in vascularized composite allotransplantation

Anggelia, Madonna Rica; Cheng, Hui-Yun; Lai, Ping-Chin; Hsieh, Yun-Huan; Lin, Chih‐Hung; Lin, Chih‐Hung

doi:10.1016/j.bj.2022.01.005

Cited by 14 publications

(8 citation statements)

References 85 publications

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“…The transplanted VBM replenishes donor-derived hematopoietic progenitor cells and provides trophic factors to support BM replication to generate chimerism ( 22 ). Moreover, hematopoietic stem cells and stromal mesenchymal stem cells may prevent rejection ( 23 ). Our recent study demonstrated a similar efficacy of inducing donor-specific tolerance by VBM transplantation when compared to 1.5 × 10 8 cells of BM transplantation in a mouse model ( 9 ).…”

Section: Discussionmentioning

confidence: 99%

The intragraft vascularized bone marrow induces secondary donor-specific mystacial pad allograft tolerance

et al. 2022

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IntroductionVascularized bone marrow (VBM) is essential in tolerance induction through chimerism. We hypothesized that the inclusion of VBM contributes to the induction of mystacial pad allotransplantation tolerance.MethodIn this study, 19 VBM, nine mystacial pad, and six sequential VBM and mystacial pad allografts were transplanted from Brown Norway (BN) rats to Lewis (LEW) rats to test our hypothesis. The VBM recipients were divided into antilymphocyte serum (ALS) monotherapy group (two doses of ALS on day 3 pretransplantation and day 1 posttransplantation), immunosuppressant group [a week of 2 mg/kg/day tacrolimus (Tac) and 3 weeks of 3 mg/kg/day rapamycin (RPM)], and combined therapy group. The mystacial pad recipients were divided into VBM and non-VBM transplantation groups, and both groups were treated with an immunosuppression regimen that consists of ALS, Tac, and RPM. For the recipients of sequential VBM and mystacial pad allotransplantations, additional Tac was given 1 week after mystacial pad transplantation. Allograft survival, donor-specific tolerance, and chimerism level were evaluated.ResultsWith the administration of ALS and short-term Tac and RPM treatments, VBM recipients demonstrated long-term graft survival (>120 days) with persistent chimerism for 30 days. CD3+ T cells from tolerant rats showed donor-specific hyporesponsiveness and tolerance to donor skin grafts but not to third-party counterparts. Furthermore, mystacial pad graft recipients with VBM transplantation exhibited a higher allograft survival rate than those without VBM transplantation [median survival time (MST) >90 days vs. 70 days, p < 0.05].ConclusionThis study demonstrated that VBM transplantation is an efficient strategy to induce and maintain donor-specific tolerance for an osseous-free allograft.

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Section: Discussionmentioning

confidence: 99%

The intragraft vascularized bone marrow induces secondary donor-specific mystacial pad allograft tolerance

et al. 2022

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“…Tregs, comprising 5-7% of CD4 þ T cells, play a crucial role in immune homeostasis by counterbalancing harmful immune responses [62,63]. There are two ways to employ Tregs as cell-based therapy: expanding Treg numbers and directing them to specific locations using pharmacological agents [2,[81][82][83][84] or expanding recipient or third-party Tregs for adoptive transfer [64,65]. Studies have shown that Tregs from tolerant recipients can rescue allografts from rejection, emphasizing their significance in the early posttransplant phase [66].…”

Section: Regulatory T-cells Applications In Vascularized Composite Al...mentioning

confidence: 99%

“…The choice of timing may depend on the immunosuppressive protocols used during different VCA phases [80]. Dividing cell doses and repeated administration have shown better tolerogenic outcomes compared to a single bolus injection, suggesting the frequency of injections can optimize therapeutic effects of cell-based therapies [81][82][83].…”

Section: Timing and Frequency Of Cell Therapymentioning

confidence: 99%

“…The route of administration is crucial and has three main options: intravenous, intraosseous, and local (directly into the allograft tissue). Intravenous injection is commonly used, but cells can get trapped in the lung and reticuloendothelial system capillaries [68,83]. Siemionow et al reported that Intraosseous injection has shown superiority over intravenous for bone marrow derived MSCs, DRCC or hematopoietic stem cells [84][85][86].…”

Section: Route Of Administrationmentioning

confidence: 99%

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Novel cell-based strategies for immunomodulation in vascularized composite allotransplantation

Siemionow,

Kulahci,

Zor

2023

Current Opinion in Organ Transplantation

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Purpose of review Vascularized composite allotransplantation (VCA) has become a clinical reality in the past two decades. However, its routine clinical applications are limited by the risk of acute rejection, and the side effects of the lifelong immunosuppression. Therefore, there is a need for new protocols to induce tolerance and extend VCA survival. Cell- based therapies have emerged as an attractive strategy for tolerance induction in VCA. This manuscript reviews the current strategies and applications of cell-based therapies for tolerance induction in VCA. Recent findings Cellular therapies, including the application of bone marrow cells (BMC), mesenchymal stem cells (MSC), adipose stem cells, regulatory T cells (Treg) cells, dendritic cells and donor recipient chimeric cells (DRCC) show promising potential as a strategy to induce tolerance in VCA. Ongoing basic science research aims to provide insights into the mechanisms of action, homing, functional specialization and standardization of these cellular therapies. Additionally, translational preclinical and clinical studies are underway, showing encouraging outcomes. Summary Cellular therapies hold great potential and are supported by preclinical studies and clinical trials demonstrating safety and efficacy. However, further research is needed to develop novel cell-based immunosuppressive protocol for VCA.

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“…It poses a reliable treatment approach for patients who underwent significant tissue loss. Anggelia and team review the current use of cell therapy to improve allograft outcome, and conclude that the suitable type of therapy is clinically dependent for instance on the allograft phase [ 17 ].…”

Section: Also In This Issuementioning

confidence: 99%

A finger in every pie – The versatility of chemokines

Kattner¹

2022

Biomedical Journal

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Cell therapy in vascularized composite allotransplantation

Cited by 14 publications

References 85 publications

The intragraft vascularized bone marrow induces secondary donor-specific mystacial pad allograft tolerance

The intragraft vascularized bone marrow induces secondary donor-specific mystacial pad allograft tolerance

Novel cell-based strategies for immunomodulation in vascularized composite allotransplantation

A finger in every pie – The versatility of chemokines

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