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Adipocyte-derived stem cell-based gene therapy upon adipogenic differentiation on microcarriers attenuates type 1 diabetes in mice.
Stem Cell Res Ther 2019; 10(1):36SC

Abstract

BACKGROUND

Insulin replenishment is critical for patients with type 1 diabetes; however, current treatments such as pancreatic islet transplantation and insulin injection are not ideal. In addition to stem cell or gene therapy alone, stem cell combined with gene therapy may provide a new route for insulin replenishment, which could avoid an autoimmune reaction against differentiated β cells or systematic viral vector injection.

METHODS

In this study, human adipocyte-derived stem cells (ADSCs) were transducted with lentiviral vectors expressing a furin-cleavable insulin gene. The expression levels of insulin were measured before and after adipogenic differentiation in the presence or absence of an adipocyte-specific promoter AP2. In vitro proliferation and in vivo survival of cells were examined on cytodex and cytopore microcarriers. The effect of ADSC-based gene therapy upon adipogenic differentiation on microcarriers was evaluated in the streptozotocin-induced type 1 diabetic mouse model.

RESULTS

We found that differentiation of ADSCs into adipocytes increased insulin expression under the EF1 promoter, while adipocyte-specific AP2 promoter further increased insulin expression upon differentiation. The microcarriers supported cell attachment and proliferation during in vitro culture and facilitate cell survival after transplantation. Functional cells on the cytopore 1 microcarrier formed tissue-like structures and alleviated hyperglycemia in the type 1 diabetic mice after subcutaneous injection.

CONCLUSIONS

Our results indicated that differentiation of ADSC and tissue-specific promotors may enhance the expression of therapeutic genes. The use of microcarriers may facilitate cell survival after transplantation and hold potential for long-term cell therapy.

Authors+Show Affiliations

Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, 100029, People's Republic of China.Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, 100029, People's Republic of China.College of Chemical and Pharmaceutical Engineering, Hebei University of Science and Technology, Shijiazhuang, 050018, People's Republic of China. Research Center for Translational Medicine, Cancer Stem Cell Institute, East Hospital, Tongji University School of Medicine, Shanghai, 200120, People's Republic of China.Department of Plastic Surgery, China-Japan Friendship Hospital, Beijing, 100029, People's Republic of China.Department of General Surgery, China-Japan Friendship Hospital, Beijing, 100029, People's Republic of China.Beijing University of Chinese Medicine, Beijing, 100029, People's Republic of China. The 2nd Department of Pulmonary Disease in TCM, The Key Unit of SATCM Pneumonopathy Chronic Cough and Dyspnea, Beijing Key Laboratory of Prevention and Treatment of Allergic Diseases with TCM (No. BZ0321), Center of Respiratory Medicine, China-Japan Friendship Hospital; National Clinical Research Center for Respiratory Diseases, Beijing, 100029, People's Republic of China.Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, 100029, People's Republic of China.Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, 100029, People's Republic of China.Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, 100029, People's Republic of China. wzai_163pass@163.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30670068

Citation

Fang, Qing, et al. "Adipocyte-derived Stem Cell-based Gene Therapy Upon Adipogenic Differentiation On Microcarriers Attenuates Type 1 Diabetes in Mice." Stem Cell Research & Therapy, vol. 10, no. 1, 2019, p. 36.
Fang Q, Zhai M, Wu S, et al. Adipocyte-derived stem cell-based gene therapy upon adipogenic differentiation on microcarriers attenuates type 1 diabetes in mice. Stem Cell Res Ther. 2019;10(1):36.
Fang, Q., Zhai, M., Wu, S., Hu, X., Hua, Z., Sun, H., ... Wang, Z. (2019). Adipocyte-derived stem cell-based gene therapy upon adipogenic differentiation on microcarriers attenuates type 1 diabetes in mice. Stem Cell Research & Therapy, 10(1), p. 36. doi:10.1186/s13287-019-1135-y.
Fang Q, et al. Adipocyte-derived Stem Cell-based Gene Therapy Upon Adipogenic Differentiation On Microcarriers Attenuates Type 1 Diabetes in Mice. Stem Cell Res Ther. 2019 01 22;10(1):36. PubMed PMID: 30670068.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Adipocyte-derived stem cell-based gene therapy upon adipogenic differentiation on microcarriers attenuates type 1 diabetes in mice. AU - Fang,Qing, AU - Zhai,Min, AU - Wu,Shan, AU - Hu,Xiaogen, AU - Hua,Zhan, AU - Sun,Huizhuo, AU - Guo,Jing, AU - Zhang,Wenjian, AU - Wang,Zai, Y1 - 2019/01/22/ PY - 2018/08/28/received PY - 2019/01/06/accepted PY - 2018/12/13/revised PY - 2019/1/24/entrez PY - 2019/1/24/pubmed PY - 2019/1/24/medline KW - Adipocyte-derived stem cell KW - Adipogenic differentiation KW - Diabetes KW - Gene therapy KW - Microcarrier SP - 36 EP - 36 JF - Stem cell research & therapy JO - Stem Cell Res Ther VL - 10 IS - 1 N2 - BACKGROUND: Insulin replenishment is critical for patients with type 1 diabetes; however, current treatments such as pancreatic islet transplantation and insulin injection are not ideal. In addition to stem cell or gene therapy alone, stem cell combined with gene therapy may provide a new route for insulin replenishment, which could avoid an autoimmune reaction against differentiated β cells or systematic viral vector injection. METHODS: In this study, human adipocyte-derived stem cells (ADSCs) were transducted with lentiviral vectors expressing a furin-cleavable insulin gene. The expression levels of insulin were measured before and after adipogenic differentiation in the presence or absence of an adipocyte-specific promoter AP2. In vitro proliferation and in vivo survival of cells were examined on cytodex and cytopore microcarriers. The effect of ADSC-based gene therapy upon adipogenic differentiation on microcarriers was evaluated in the streptozotocin-induced type 1 diabetic mouse model. RESULTS: We found that differentiation of ADSCs into adipocytes increased insulin expression under the EF1 promoter, while adipocyte-specific AP2 promoter further increased insulin expression upon differentiation. The microcarriers supported cell attachment and proliferation during in vitro culture and facilitate cell survival after transplantation. Functional cells on the cytopore 1 microcarrier formed tissue-like structures and alleviated hyperglycemia in the type 1 diabetic mice after subcutaneous injection. CONCLUSIONS: Our results indicated that differentiation of ADSC and tissue-specific promotors may enhance the expression of therapeutic genes. The use of microcarriers may facilitate cell survival after transplantation and hold potential for long-term cell therapy. SN - 1757-6512 UR - https://www.unboundmedicine.com/medline/citation/30670068/Adipocyte-derived_stem_cell-based_gene_therapy_upon_adipogenic_differentiation_on_microcarriers_attenuates_type_1_diabetes_in_mice DB - PRIME DP - Unbound Medicine ER -