Stivers Katlin B, Beare Jason E, Chilton Paula M, Williams Stuart K, Kaufman Christina L, Hoying James B
aCardiovascular Innovation InstitutebDepartment of Microbiology & Immunology, University of LouisvillecChristine M. Kleinert Institute for Hand and Microsurgery, Louisville, Kentucky, USA.
Curr Opin Organ Transplant. 2017 Oct;22(5):490-498. doi: 10.1097/MOT.0000000000000452.
Controlling acute allograft rejection following vascularized composite allotransplantation requires strict adherence to courses of systemic immunosuppression. Discovering new methods to modulate the alloreactive immune response is essential for widespread application of vascularized composite allotransplantation. Here, we discuss how adipose-derived cellular therapies represent novel treatment options for immune modulation and tolerance induction in vascularized composite allotransplantation.
Adipose-derived mesenchymal stromal cells are cultured from autologous or allogeneic adipose tissue and possess immunomodulatory qualities capable of prolonging allograft survival in animal models of vascularized composite allotransplantation. Similar immunosuppressive and immunomodulatory effects have been observed with noncultured adipose stromal-vascular-fraction-derived therapies, albeit publication of in-vivo stromal vascular fraction cell modulation in transplantation models is lacking. However, both stromal vascular fraction and adipose derived mesenchymal stem cell therapies have the potential to effectively modulate acute allograft rejection via recruitment and induction of regulatory immune cells.
To date, most reports focus on adipose derived mesenchymal stem cells for immune modulation in transplantation despite their phenotypic plasticity and reliance upon culture expansion. Along with the capacity for immune modulation, the supplemental wound healing and vasculogenic properties of stromal vascular fraction, which are not shared by adipose derived mesenchymal stem cells, hint at the profound therapeutic impact stromal vascular fraction-derived treatments could have on controlling acute allograft rejection and tolerance induction in vascularized composite allotransplantation. Ongoing projects in the next few years will help design the best applications of these well tolerated and effective treatments that should reduce the risk/benefit ratio and allow more patients access to vascularized composite allotransplantation therapy.
在血管化复合组织移植后控制急性移植物排斥反应需要严格遵循全身免疫抑制疗程。发现调节同种异体反应性免疫应答的新方法对于血管化复合组织移植的广泛应用至关重要。在此，我们讨论脂肪来源的细胞疗法如何代表血管化复合组织移植中免疫调节和诱导耐受的新型治疗选择。
脂肪来源的间充质基质细胞从自体或异体脂肪组织中培养而来，具有免疫调节特性，能够在血管化复合组织移植的动物模型中延长移植物存活时间。在未经培养的脂肪基质血管成分衍生疗法中也观察到了类似的免疫抑制和免疫调节作用，尽管缺乏在移植模型中体内基质血管成分细胞调节的相关报道。然而，基质血管成分和脂肪来源的间充质干细胞疗法都有可能通过募集和诱导调节性免疫细胞来有效调节急性移植物排斥反应。
迄今为止，尽管脂肪来源的间充质干细胞具有表型可塑性且依赖培养扩增，但大多数报道仍聚焦于其在移植中的免疫调节作用。除了免疫调节能力外，基质血管成分所具有的补充伤口愈合和血管生成特性是脂肪来源的间充质干细胞所不具备的，这暗示了基质血管成分衍生疗法在控制血管化复合组织移植中的急性移植物排斥反应和诱导耐受方面可能具有深远的治疗影响。未来几年正在进行的项目将有助于设计这些耐受性良好且有效的治疗方法的最佳应用，这应该会降低风险/效益比，并使更多患者能够接受血管化复合组织移植治疗。
