Donor-dependent variation of human umbilical cord blood mesenchymal stem cells in response to hypoxic preconditioning and amelioration of limb ischemia

被引:60
作者
Kang, Insung [1 ,2 ]
Lee, Byung-Chul [1 ,2 ]
Choi, Soon Won [1 ,2 ]
Lee, Jin Young [1 ,2 ]
Kim, Jae-Jun [1 ,2 ]
Kim, Bo-Eun [1 ,2 ]
Kim, Da-Hyun [1 ,2 ]
Lee, Seung Eun [1 ,2 ]
Shin, Nari [1 ,2 ]
Seo, Yoojin [1 ,3 ,4 ]
Kim, Hyung-Sik [1 ,3 ,4 ]
Kim, Dong-Ik [5 ]
Kang, Kyung-Sun [1 ,2 ]
机构
[1] Seoul Natl Univ, Coll Vet Med, Adult Stem Cell Res Ctr, Seoul 08826, South Korea
[2] Seoul Natl Univ, Res Inst Vet Med, Coll Vet Med, Seoul 08826, South Korea
[3] Pusan Natl Univ, Sch Med, Busan 49241, South Korea
[4] Pusan Natl Univ Hosp, Biomed Res Inst, Busan 49241, South Korea
[5] Sungkyunkwan Univ, Div Vasc Surg, Samsung Med Ctr, Sch Med, Seoul 06351, South Korea
基金
新加坡国家研究基金会;
关键词
PERIPHERAL ARTERIAL-DISEASE; ANGIOGENESIS; EXPRESSION; THERAPY; PERFUSION; GROWTH; MODEL; VEGF;
D O I
10.1038/s12276-017-0014-9
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
With the rapidly growing demand for mesenchymal stem cell (MSC) therapy, numerous strategies using MSCs for different diseases have been studied and reported. Because of their immunosuppressive properties, MSCs are commonly used as an allogeneic treatment. However, for the many donors who could potentially be used, it is important to understand the capacity for therapeutic usage with donor-to-donor heterogeneity. In this study, we aimed to investigate MSCs as a promising therapeutic strategy for critical limb ischemia. We evaluated MSCs from two donors (#55 and #64) and analyzed the capacity for angiogenesis through in vivo and in vitro assays to compare the therapeutic effect between different donors. We emphasized the importance of intra-population heterogeneity of MSCs on therapeutic usage by evaluating the effects of hypoxia on activating cellular angiogenesis in MSCs. The precondition of hypoxia in MSCs is known to enhance therapeutic efficacy. Our study suggests that sensitivity to hypoxic conditions is different between cells originating from different donors, and this difference affects the contribution to angiogenesis. The bioinformatics analysis of different donors under hypoxic culture conditions identified intrinsic variability in gene expression patterns and suggests alternative potential genetic factors ANGPTL4, ADM, SLC2A3, and CDON as guaranteed general indicators for further stem cell therapy.
引用
收藏
页码:1 / 15
页数:15
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