Serially Transplanted Nonpericytic CD146(-) Adipose Stromal/Stem Cells in Silk Bioscaffolds Regenerate Adipose Tissue In Vivo.
Serially Transplanted Nonpericytic CD146(-) Adipose Stromal/Stem Cells in Silk Bioscaffolds Regenerate Adipose Tissue In Vivo.
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DOI：
10.1002/stem.2325
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发表时间：
2016-04
期刊：
影响因子：
--
通讯作者：
Gimble JM
中科院分区：
文献类型：
--
作者：
Frazier TP;Bowles A;Lee S;Abbott R;Tucker HA;Kaplan D;Wang M;Strong A;Brown Q;He J;Bunnell BA;Gimble JM
来源于白色脂肪组织（WAT）的间质血管组分（SVF）的祖细胞具有形成克隆群体并沿沿着多个谱系途径分化的能力。然而，文献继续在将脂肪祖细胞定义为“基质”或“干”细胞之间摇摆不定。最近的研究表明，脂肪基质细胞的非周细胞亚群，具有表型，CD 45 −/CD 31 −/CD 146 −/CD 34+，是间充质细胞，并表明这可能是脂肪组织内的内源性祖细胞亚群。我们假设脂肪祖细胞可以根据CD 146、CD 34和/或CD 29的表达进行分选，并且当植入体内时，这些细胞可以在连续移植中持续存在、增殖和再生功能性脂肪垫。通过流式细胞术对基质血管部分（SVF）细胞和广泛表达GFP转基因（GFP-Tg）的培养扩增的脂肪基质/干细胞（ASC）进行分级。将新鲜分离的SVF和培养扩增的ASC接种在三维丝支架中，皮下植入野生型宿主中，并连续移植。取出六周WAT构建体并评估GFP-Tg脂肪细胞和干细胞的存在。流式细胞术，定量聚合酶链反应，共聚焦显微镜证明GFP-Tg细胞的持久性，增殖和扩张，分别。甘油分泌和葡萄糖摄取测定显示GFP-Tg脂肪具有代谢功能。与未接种的对照相比，接种GFP-Tg SVF细胞或GFP-Tg ASC的构建体显示出消化组织的SVF产量更高，并且构建体重量更高。与未分选的或CD 29 + GFP-Tg ASC对应物相比，来自CD 146 − CD 34+富集的GFP-Tg ASC群体的构建体表现出更高的血红蛋白饱和度和更高的GFP-Tg细胞频率。这些数据证明了非周细胞脂肪来源的祖细胞的成功连续移植，其可以将脂肪组织重建为实体器官。这些发现有可能为脂肪祖细胞的干细胞身份提供新的见解。
Progenitors derived from the stromal vascular fraction (SVF) of white adipose tissue (WAT) possess the ability to form clonal populations and differentiate along multiple lineage pathways. However, the literature continues to vacillate between defining adipocyte progenitors as “stromal” or “stem” cells. Recent studies have demonstrated that a non-pericytic subpopulation of adipose stromal cells, which possess the phenotype, CD45−/CD31−/CD146−/CD34+, are mesenchymal, and suggest this may be an endogenous progenitor subpopulation within adipose tissue. We hypothesized that an adipose progenitor could be sorted based on the expression of CD146, CD34, and/or CD29 and when implanted in vivo these cells can persist, proliferate, and re-generate a functional fat pad over serial transplants. Stromal vascular fraction (SVF) cells and culture expanded adipose stromal/stem cells (ASC) ubiquitously expressing the GFP transgene (GFP-Tg) were fractionated by flow cytometry. Both freshly isolated SVF and culture expanded ASC were seeded in 3-dimensional silk scaffolds, implanted subcutaneously in wild type hosts, and serially transplanted. Six week WAT constructs were removed and evaluated for the presence of GFP-Tg adipocytes and stem cells. Flow cytometry, quantitative polymerase chain reaction, and confocal microscopy demonstrated GFP-Tg cell persistence, proliferation, and expansion, respectively. Glycerol secretion and glucose uptake assays revealed GFP-Tg adipose was metabolically functional. Constructs seeded with GFP-Tg SVF cells or GFP-Tg ASC exhibited higher SVF yields from digested tissue, and higher construct weights, compared to non-seeded controls. Constructs derived from CD146− CD34+ -enriched GFP-Tg ASC populations exhibited higher hemoglobin saturation, and higher frequency of GFP-Tg cells than unsorted or CD29+ GFP-Tg ASC counterparts. These data demonstrated successful serial transplantation of non-pericytic adipose derived progenitors that can reconstitute adipose tissue as a solid organ. These findings have the potential to provide new insights regarding the stem cell identity of adipose progenitor cells.
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影响因子：
4.9
作者：
Maumus, M.;Peyrafitte, J-A;D'Angelo, R.;Fournier-Wirth, C.;Bouloumie, A.;Casteilla, L.;Sengenes, C.;Bourin, P.
通讯作者：
Bourin, P.
DOI：
10.1002/oby.20671
发表时间：
2014-04
期刊：
Obesity (Silver Spring, Md.)
影响因子：
--
作者：
Gawronska-Kozak B;Staszkiewicz J;Gimble JM;Kirk-Ballard H
通讯作者：
Kirk-Ballard H
影响因子：
3.6
作者：
Li H;Zimmerlin L;Marra KG;Donnenberg VS;Donnenberg AD;Rubin JP
通讯作者：
Rubin JP
影响因子：
3.7
作者：
Kim JH;Jee MK;Lee SY;Han TH;Kim BS;Kang KS;Kang SK
通讯作者：
Kang SK
影响因子：
15.9
作者：
Crossno, Joseph T., Jr.;Majka, Susan M.;Klemm, Dwight J.
通讯作者：
Klemm, Dwight J.