The immunogenicity of human adipose-derived cells: Temporal changes in vitro

The immunogenicity of human adipose-derived cells: Temporal changes in vitro
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DOI:
10.1634/stemcells.2005-0235
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发表时间:
2006-05-01
期刊:
影响因子:
5.2
通讯作者:
Gimble, Jeffrey M.
Gimble, Jeffrey M.
中科院分区:
医学2区
文献类型:
--
作者:
McIntosh, Kevin;Zvonic, Sanjin;Gimble, Jeffrey M.

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再生医学技术将需要大量的人类成体干细胞来源,这些干细胞可以在护理点随时获得。使用不匹配的异基因干细胞的能力将有助于实现这一目标。由于脂肪组织代表了一个未开发的人类细胞库,我们比较了新鲜分离的胶原酶消化的人脂肪组织来源的基质血管部分细胞(SVFs)相对于传代的塑料贴壁脂肪来源的干细胞(ASC)的免疫原性。平行研究表明,粘附到塑料和随后的人类脂肪来源的细胞的扩增选择一个相对同质的细胞群体的免疫表型的基础上。与这些发现一致,在异源SVF细胞群上检测到的造血相关标志物(CD 11 a、CD 14、CD 45、CD 86和组织相容性位点抗原-DR [HLA-DR])的存在在ASC随后传代时减少。在混合淋巴细胞反应(MLR)中,SVF和早期传代ASC刺激同种异体应答T细胞的增殖。相反,超过P1代的ASC未能引起T细胞的应答。事实上,晚代ASC实际上抑制了MLR反应。尽管这些结果支持同种异体人ASC移植的可行性,但仍需要进行体内动物研究的证实。
Regenerative medical techniques will require an abundant source of human adult stem cells that can be readily available at the point of care. The ability to use unmatched allogeneic stem cells will help achieve this goal. Since adipose tissue represents an untapped reservoir of human cells, we have compared the immunogenic properties of freshly isolated, collagenase-digested human adipose tissue-derived stromal vascular fraction cells (SVFs) relative to passaged, plastic-adherent adipose-derived stem cells (ASCs). Parallel studies have shown that adherence to plastic and subsequent expansion of human adipose-derived cells selects for a relatively homogeneous cell population based on immunophenotype. Consistent with these findings, the presence of hematopoietic-associated markers (CD11a, CD14, CD45, CD86, and histocompatible locus antigen-DR [HLA-DR]) detected on the heterogeneous SVF cell population decreased upon subsequent passage of the ASCs. In mixed lymphocyte reactions (MLRs), SVFs, and early passage ASCs stimulated proliferation by allogeneic responder T cells. In contrast, the ASCs beyond passage P1 failed to elicit a response from T cells. Indeed, late passage ASCs actually suppressed the MLR response. Although these results support the feasibility of allogeneic human ASC transplantation, confirmatory in vivo animal studies will be required.