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Updated: May 23, 2026
Creation and Transplantation of an Adipose-derived Stem Cell (ASC) Sheet in a Diabetic Wound-healing Model
Published on: August 4, 2017
Genetic modification of human adipose-derived stem cells for promoting wound healing
Seung-Hyun Song1, Mi-Ok Lee, Ji-Seon Lee
1Department of Life Sciences, College of Natural Sciences, Sogang University, Seoul, Republic of Korea.
Background:
Diverse growth factors secreted from human adipocyte-derived stem cells (hASCs) that support or manage adjacent cells have been studied for therapeutic potentials to a variety of pathological models. However, senescent growth arrest in hASCs during in vitro culture and subsequent defective differentiation potential, have been technical barriers to further genetic modification of hASCs for functional improvement.
Objective:
We investigated the feasibility of long-term hASC culture to enhance their therapeutic use.
Methods:
We used a MYC variant to generate hASCs expressing v-myc and determined their growth potential and growth factor secretion profile. We further introduced an AKT variant to generate constitutively active (CA)-Akt/v-myc hASCs. Finally, we tested the ability of promoting wound healing of medium conditioned with CA-Akt/v-myc hASCs.
Results:
The v-myc hASCs actively proliferated longer than control hASCs. Increased secretion of vascular endothelial growth factor (VEGF) by v-myc hASCs promoted the migration potential of hASCs and vasculogenesis in co-cultured endothelial cells. Additional genetic modification of v-myc hASCs using CA-Akt further increased VEGF secretion. In addition, injection of CA-Akt/v-myc hASCs-CM into wound-mice model promoted wound healing compared to normal hASCs-CM.
Conclusion:
Genetic modification of hASCs to stimulate secretion of growth factors is a novel strategy to maximize their paracrine effect and improve their therapeutic potential.
Insights
Genetic modification of human adipocyte-derived stem cells (hASCs) enhances their therapeutic potential. Engineering hASCs with MYC and AKT variants boosts growth factor secretion, improving wound healing capabilities.
Area of Science:
- Stem cell biology
- Regenerative medicine
- Genetic engineering
Background:
- Human adipocyte-derived stem cells (hASCs) secrete growth factors with therapeutic potential.
- In vitro culture leads to hASC senescence and impaired differentiation, limiting their use.
- Genetic modification strategies are needed to overcome these limitations.
Purpose of the Study:
- To investigate the feasibility of long-term hASC culture for enhanced therapeutic applications.
- To genetically modify hASCs to improve their growth potential and therapeutic efficacy.
Main Methods:
- Generated v-myc hASCs using a MYC variant to assess growth and secretion.
- Created constitutively active (CA)-Akt/v-myc hASCs by introducing an AKT variant.
- Evaluated the wound healing potential of conditioned medium from modified hASCs in a mouse model.
Main Results:
- v-myc hASCs exhibited prolonged proliferation compared to controls.
- Increased vascular endothelial growth factor (VEGF) secretion by v-myc hASCs enhanced hASC migration and endothelial cell vasculogenesis.
- CA-Akt modification further boosted VEGF secretion.
- Conditioned medium from CA-Akt/v-myc hASCs significantly promoted wound healing in mice.
Conclusions:
- Genetic modification of hASCs to stimulate growth factor secretion is a viable strategy.
- This approach maximizes the paracrine effect of hASCs.
- Enhanced paracrine signaling improves the therapeutic potential of hASCs for regenerative applications.
