Advances in mesenchymal stem cells promoting the efficacy of islet transplantation

doi:10.3877/cma.j.issn.2095-1221.2024.06.005

Abstract

Abstract:

Islet transplantation is the most effective method to restore endogenous insulin secretion and control blood glucose， but there are still problems such as low survival rate， decline of long-term function and immune rejection of islet grafts. Mesenchymal stem cells （MSCs） have attracted much attention due to their ability to secrete the extracellular matrix （ECM） with a variety of cytokines， or promoting the restoration of cellular injury， angiogenesis and anti-inflammatory effects through direct cell-cell interaction. MSCs for islet transplantation has the advantages of wide source，low immunogenicity， and can effectively solve the problems of low survival rate， poor function and immune response of islet grafts， so they has become a research hotspot in islet transplantation. This paper reviews progress in MSCs in islet transplantation， including the role of MSCs and their secreted cytokines in islet culture in vitro， transplantation research in vivo and clinical application， as well as the problems in the application of MSCs， aiming to further promote the application of MSCs in clinical islet transplantation.

Key words: Mesenchymal stem cells, Conditioned media, Extracellular matrix, Cytokines, Islet transplantation

Hongxing Fu, Zhikai Wang, Guilin Xie, Juanjuan Cai, Wei Yang, Sheng Yan. Advances in mesenchymal stem cells promoting the efficacy of islet transplantation[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2024, 14(06): 351-360.

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	静脉注射途径（IVR）	肾包膜下（KSR）	皮下途径（SQR）
安全性	（1）有侵入性；（2）腹部手术，经门静脉注射，有感染风险	（1）有侵入性；（2）有感染的风险，从肾被膜下取出输注器时有泄漏的风险^［72］	（1）创伤小；（2）感染风险小；（3）有注射部位脓肿风险
机理	间接接触，MSCs随着血流迁移，进入非靶器官，通过体液因子对胰岛发挥保护作用^［13］	MSCs改变了趋化因子和细胞因子的分泌谱，改变了脾脏和血液中T-reg和T辅助细胞的平衡^{［61，73］}	间接接触，MSCs形成多细胞聚集，很少迁移，通过细胞因子对胰岛发挥保护作用^［74］
有效性	（1）对胰岛移植物有保护作用；（2）MSCs迁移受限，受肺部滞留的影响	（1）需要降低MSCs对胰岛的比例，早期血管化增加，胰岛功能增强^［73］；（2）是免疫特惠位点^［61-62］	（1）异体胰岛易引起排斥；（2）皮下组织血管化不良，移植物不易存活，胰岛素水平较高^［74-75］

	静脉注射途径（IVR）	肾包膜下（KSR）	皮下途径（SQR）
安全性	（1）有侵入性；（2）腹部手术，经门静脉注射，有感染风险	（1）有侵入性；（2）有感染的风险，从肾被膜下取出输注器时有泄漏的风险^［72］	（1）创伤小；（2）感染风险小；（3）有注射部位脓肿风险
机理	间接接触，MSCs随着血流迁移，进入非靶器官，通过体液因子对胰岛发挥保护作用^［13］	MSCs改变了趋化因子和细胞因子的分泌谱，改变了脾脏和血液中T-reg和T辅助细胞的平衡^{［61，73］}	间接接触，MSCs形成多细胞聚集，很少迁移，通过细胞因子对胰岛发挥保护作用^［74］
有效性	（1）对胰岛移植物有保护作用；（2）MSCs迁移受限，受肺部滞留的影响	（1）需要降低MSCs对胰岛的比例，早期血管化增加，胰岛功能增强^［73］；（2）是免疫特惠位点^［61-62］	（1）异体胰岛易引起排斥；（2）皮下组织血管化不良，移植物不易存活，胰岛素水平较高^［74-75］

	BM-MSCs	UC-MSCs	AD-MSCs
来源	骨髓基质	脐带华通氏胶	脂肪组织
获取时间	任何时候	婴儿出生时	任何时候
分离操作	（1）有侵入性、痛苦，老年人体内难以提取；（2）与潜在的供体部位发病率相关；（3）产量低	（1）无创、无痛；（2）酶消化；（3）产量极低^{［112-113］}	（1）微创、安全、技术完善；（2）酶消化；含有其他细胞的混合物；（3）产量高，无需体外扩增^［114］
增殖能力和分化潜能	（1）增殖能力相对最低；（2）成骨分化相关基因表达相对较高；（3）基因上稳定；（4）分化潜能上有争议	（1）增殖能力相对最高；（2）与血管生成相关的基因相对表达更高；（3）在长期培养中保持表型和遗传稳定性；（4）扩增时间短，高增殖性，克隆性强	（1）增殖能力高；（2）与血管生成相关的基因相对高表达；（3）在基因和形态上保持稳定；（4）在长期培养中保持分化潜能
免疫表型和免疫调节活性	（1）低免疫原性；（2）高表达CD106、CD49f、Podxl，不表达CD34；（3）对Ig产生的抑制程度较小；（4）对防止血液单核细胞转化为树突状细胞和成熟树突状细胞共刺激分子的表达影响较小^［115］	（1）低免疫原性；（2）不表达CD34；（3）通过刺激B细胞增殖和B细胞免疫球蛋白产生的旁分泌作用；（4）通过诱导T细胞凋亡和细胞周期阻滞来抑制效应T细胞^［116］	（1）低免疫原性；（2）表达CD49d、CD54，不表达CD106、CD49f、Podxl；（3）更抑制Ig的产生；（4）阻止单核细胞转化为树突状细胞，并从成熟的树突状细胞中表达共刺激分子，即更有效的免疫抑制因子^［115］

	BM-MSCs	UC-MSCs	AD-MSCs
来源	骨髓基质	脐带华通氏胶	脂肪组织
获取时间	任何时候	婴儿出生时	任何时候
分离操作	（1）有侵入性、痛苦，老年人体内难以提取；（2）与潜在的供体部位发病率相关；（3）产量低	（1）无创、无痛；（2）酶消化；（3）产量极低^{［112-113］}	（1）微创、安全、技术完善；（2）酶消化；含有其他细胞的混合物；（3）产量高，无需体外扩增^［114］
增殖能力和分化潜能	（1）增殖能力相对最低；（2）成骨分化相关基因表达相对较高；（3）基因上稳定；（4）分化潜能上有争议	（1）增殖能力相对最高；（2）与血管生成相关的基因相对表达更高；（3）在长期培养中保持表型和遗传稳定性；（4）扩增时间短，高增殖性，克隆性强	（1）增殖能力高；（2）与血管生成相关的基因相对高表达；（3）在基因和形态上保持稳定；（4）在长期培养中保持分化潜能
免疫表型和免疫调节活性	（1）低免疫原性；（2）高表达CD106、CD49f、Podxl，不表达CD34；（3）对Ig产生的抑制程度较小；（4）对防止血液单核细胞转化为树突状细胞和成熟树突状细胞共刺激分子的表达影响较小^［115］	（1）低免疫原性；（2）不表达CD34；（3）通过刺激B细胞增殖和B细胞免疫球蛋白产生的旁分泌作用；（4）通过诱导T细胞凋亡和细胞周期阻滞来抑制效应T细胞^［116］	（1）低免疫原性；（2）表达CD49d、CD54，不表达CD106、CD49f、Podxl；（3）更抑制Ig的产生；（4）阻止单核细胞转化为树突状细胞，并从成熟的树突状细胞中表达共刺激分子，即更有效的免疫抑制因子^［115］

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