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Isolation and characterization of novel, highly proliferative human CD34/CD73-double-positive testis-derived stem cells for cell therapy.

ABSTRACT: Human adult stem cells are a readily available multipotent cell source that can be used in regenerative medicine. Despite many advantages, including low tumorigenicity, their rapid senescence and limited plasticity have curtailed their use in cell-based therapies. In this study, we isolated CD34/CD73-double-positive (CD34(+)/CD73(+)) testicular stromal cells (HTSCs) and found that the expression of CD34 was closely related to the cells' stemness and proliferation. The CD34(+)/CD73(+) cells grew in vitro for an extended period of time, yielding a multitude of cells (5.6×10(16) cells) without forming tumors in vivo. They also differentiated into all three germ layer lineages both in vitro and in vivo, produced cartilage more efficiently compared to bone marrow stem cells and, importantly, restored erectile function in a cavernous nerve crush injury rat model. Thus, these HTSCs may represent a promising new autologous cell source for clinical use.

SUBMITTER: Choi WY

PROVIDER: S-EPMC3715792 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Isolation and characterization of novel, highly proliferative human CD34/CD73-double-positive testis-derived stem cells for cell therapy.

Choi Won Yun WY Jeon Hwang Gyun HG Chung Young Y Lim Jung Jin JJ Shin Dong Hyuk DH Kim Jung Mo JM Ki Byeong Seong BS Song Seung-Hun SH Choi Seong-Jun SJ Park Keun-Hong KH Shim Sung Han SH Moon Jisook J Jung Sung Jun SJ Kang Hyun Mi HM Park Seah S Chung Hyung Min HM Ko Jung Jae JJ Cha Kwang Yul KY Yoon Tae Ki TK Kim Haekwon H Lee Dong Ryul DR

Stem cells and development 20130503 15

Human adult stem cells are a readily available multipotent cell source that can be used in regenerative medicine. Despite many advantages, including low tumorigenicity, their rapid senescence and limited plasticity have curtailed their use in cell-based therapies. In this study, we isolated CD34/CD73-double-positive (CD34(+)/CD73(+)) testicular stromal cells (HTSCs) and found that the expression of CD34 was closely related to the cells' stemness and proliferation. The CD34(+)/CD73(+) cells grew ...[more]

PMID: 23509942

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Project description:BackgroundReducing cutaneous scar formation is important for assessing the success of skin wound healing. Although it is generally accepted that adipose-derived mesenchymal stem cells (AMSCs) have substantial therapeutic potential, efforts are continuously made to improve the outcome of AMSC therapy. Post-transcriptional suppression of procollagen-lysine 1, 2-oxoglutarate 5-dioxygenase 1 (PLOD1) in AMSCs has been shown to greatly reduce scar formation during skin wound healing, likely through modulating macrophage polarization. In the present study, we tested whether a CD73+ subpopulation of AMSCs could reduce scar formation compared with CD73- AMSCs.MethodsThe gene profile of CD73+ versus CD73- AMSCs was obtained from a validated public database, GSE167219. AMSCs were isolated from adipose tissue surrounding the groin of mice, after which CD73+ versus CD73- AMSCs were sorted using flow cytometry. PLOD1 levels were determined in CD73+ versus CD73- AMSCs. Then, PLOD1 in CD73- AMSCs was depleted by a short-hair interfering RNA against PLOD1 (sh-PLOD1), while PLOD1 in CD73+ AMSCs was increased by expression of a PLOD1 transgene. A blade was used to induce a skin injury on the middle back of the mice. Either CD73+ AMSCs or CD73+ PLOD1 AMSCs or CD73- AMSCs or CD73- sh-PLOD1 AMSCs were intravenously transplanted into the injured region of the mice. Fibrosis and the underlying mechanisms were investigated. Co-immunoprecipitation was performed to evaluate interaction between CD73 and PLOD1.ResultsCD73+ AMSCs expressed significantly lower levels of PLOD1, a potent stimulator of fibrosis, compared with CD73- AMSCs. Transplantation of CD73+ AMSCs generated significantly reduced fibrosis at the skin injury site compared with CD73- AMSCs. However, expression of PLOD1 in CD73+ AMSCs abolished its advantageous effects on fibrosis reduction, while depletion of PLOD1 in CD73- AMSCs improved the outcome of fibrosis to the levels of transplantation of CD73+ AMSCs. Co-immunoprecipitation showed no direct protein interaction between CD73 and PLOD1.ConclusionsCD73+ AMSCs are a subgroup of AMSCs with better therapeutic effects on wound healing, and can inhibit scar formation through reduced PLOD1 in an indirect manner.

Dataset Information

Isolation and characterization of novel, highly proliferative human CD34/CD73-double-positive testis-derived stem cells for cell therapy.

Publications

Isolation and characterization of novel, highly proliferative human CD34/CD73-double-positive testis-derived stem cells for cell therapy.

Similar Datasets

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