Adipocyte-derived stem cell-based gene therapy upon adipogenic differentiation on microcarriers attenuates type 1 diabetes in mice.

Early human evidence such as case series or small samples is exploring possible benefits.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

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 microcarr

Evidence level

Early human evidence such as case series or small samples is exploring possible benefits.

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