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Conversion of adipose-derived stem cells into natural killer-like cells with anti-tumor activities in nude mice.

ABSTRACT: Efforts to develop peripheral blood-derived nature killer (NK) cells into therapeutic products have been hampered by these cells' low abundance and histoincompatibility. On the other hand, derivation of NK-like cells from more abundant cell sources such as embryonic stem cells (ESCs) and umbilical cord blood (UCB) requires the selection of rare CD34+ cells. Thus, we sought to convert adipose-derived stem cells (ADSCs), which are abundant and natively CD34+, into NK-like cells. When grown in hematopoietic induction medium, ADSCs formed sphere clusters and expressed hematopoietic markers CD34, CD45, and KDR. Further induction in NK cell-specific medium resulted in a population of cells that expressed NK cell marker CD56, and thus termed ADSC-NK. Alternatively, the hematopoietically induced ADSCs were transduced with NK cell-specific transcription factor E4BP4 prior to induction in NK cell-specific medium. This latter population of cells, termed ADSC-NKE, expressed CD56 and additional NK cell markers such as CD16, CD94, CD158, CD314, FasL, and NKp46. ADSC-NKE was as potent as NK leukemia cell NKL in killing breast cancer cell MCF7 and prostate cancer cells DU145, PC3, LnCap, DuPro, C4-2 and CWR22, but exhibited no killing activity toward normal endothelial and smooth muscle cells. In nude mice test ADSC-NKE was able to significantly delay the progression of tumors formed by MCF7 and PC3. When injected into immunocompetent rats, ADSC-NKE was detectable in bone marrow and spleen for at least 5 weeks. Together, these results suggest that ADSCs can be converted into NK-like cells with anti-tumor activities.

SUBMITTER: Ning H

PROVIDER: S-EPMC4146612 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Conversion of adipose-derived stem cells into natural killer-like cells with anti-tumor activities in nude mice.

Ning Hongxiu H Lei Hong-En HE Xu Yong-De YD Guan Rui-Li RL Venstrom Jeffrey M JM Lin Guiting G Lue Tom F TF Xin Zhongcheng Z Lin Ching-Shwun CS

PloS one 20140827 8

Efforts to develop peripheral blood-derived nature killer (NK) cells into therapeutic products have been hampered by these cells' low abundance and histoincompatibility. On the other hand, derivation of NK-like cells from more abundant cell sources such as embryonic stem cells (ESCs) and umbilical cord blood (UCB) requires the selection of rare CD34+ cells. Thus, we sought to convert adipose-derived stem cells (ADSCs), which are abundant and natively CD34+, into NK-like cells. When grown in hema ...[more]

PMID: 25162225

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Project description:BACKGROUND:Ischemic vascular diseases are the major cause of death worldwide. In recent years, endothelial cell (EC)-based approaches to vascular regeneration are increasingly viable strategies for treating ischemic diseases, but their applications are challenged by the difficulties in their efficient generation and stable maintenance. Here, we show an alternative protocol that facilitates the generation of functional and expandable ETS variant 2 (ETV2)-induced endothelial-like cells (EiECs) from human adipose-derived stem cells (hADSCs), providing a potential source of cells for autologous ECs to treat ischemic vascular diseases. METHODS:hADSCs were obtained from fresh human adipose tissue. Passage 3 hADSCs were transduced with doxycycline (DOX)-inducible ETV2 transcription factor; purified ETV2-hADSCs were induced into endothelial-like cells using a two-stage induction culture system composed of small molecule compounds and cell factors. EiECs were evaluated for their surface markers, proliferation, gene expression, secretory capacity, and effects on vascular regeneration in vivo. RESULTS:We found that short-term ETV2 expression combined with TGF-? inhibition is sufficient for the generation of kinase insert domain receptor (KDR)+ cells from hADSCs within 10?days. KDR+ cells showed immature endothelial characteristics, and they can gradually mature in a chemically defined induction medium at the second stage of induction. Futher studies showed that KDR+ cells deriving EC-like cells could stably self-renew and expand about 106-fold in 1?month, and they exhibited expected genome-wide molecular features of mature ECs. Functionally, these EC-like cells significantly promoted revascularization in a hind limb ischemic model. CONCLUSIONS:We isolated highly purified hADSCs and effectively converted them into functional and expandable endothelial-like cells. Thus, the study may provide an alternative strategy to obtain functional EC-like cells with potential for biomedical and pharmaceutical applications.

Dataset Information

Conversion of adipose-derived stem cells into natural killer-like cells with anti-tumor activities in nude mice.

Publications

Conversion of adipose-derived stem cells into natural killer-like cells with anti-tumor activities in nude mice.

Similar Datasets

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