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Diabetic Mesenchymal Stem Cells Are Ineffective for Improving Limb Ischemia Due to Their Impaired Angiogenic
Hyongbum Kim1, Ji Woong Han, Ji Yoon Lee
1Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA.
Abstract:
The purpose of this study was to investigate the effects of diabetes on mesenchymal stem cells (MSCs) in terms of their angiogenic and therapeutic potential for repairing tissue ischemia. We culture-isolated MSCs from streptozotocin-induced diabetic rats (D-MSCs) and compared their proliferation, differentiation, and angiogenic effects with those from normal rats (N-MSCs). The angiogenic effects of MSCs were evaluated by real-time PCR, in vitro tube formation assay, and transplantation of the MSCs into a hindlimb ischemia model followed by laser Doppler perfusion imaging. The number of MSCs derived from diabetic rats was smaller, and their proliferation rate was slower than N-MSCs. Upon induction of differentiation, the osteogenic and angiogenic differentiation of D-MSCs were aberrant compared to N-MSCs. The expression of angiogenic factors was lower in D-MSCs than N-MSCs. D-MSCs cocultured with endothelial cells resulted in decreased tube formation compared to N-MSCs. D-MSCs were ineffective to improve hindlimb ischemia and showed lower capillary density and angiogenic gene expression in ischemic limbs than N-MSCs. D-MSCs have defective proliferation and angiogenic activities and are ineffective for repairing hindlimb ischemia. Newer measures are needed before MSCs can be employed as a source for autologous cell therapy.
Insights
Diabetes impairs mesenchymal stem cells (MSCs), reducing their ability to promote blood vessel growth and heal tissue ischemia. Diabetic MSCs show defective proliferation and angiogenesis, limiting their therapeutic potential for conditions like hindlimb ischemia.
Area of Science:
- Biomedical Engineering
- Regenerative Medicine
- Cell Biology
Background:
- Diabetes mellitus is a complex metabolic disorder with significant implications for tissue repair and regeneration.
- Mesenchymal stem cells (MSCs) are a promising cell source for regenerative therapies due to their multipotent differentiation and immunomodulatory properties.
- The impact of diabetes on MSC function, particularly their angiogenic and therapeutic potential, requires thorough investigation for effective cell-based treatments.
Purpose of the Study:
- To investigate the effects of diabetes on the angiogenic and therapeutic potential of mesenchymal stem cells (MSCs).
- To compare the proliferation, differentiation, and angiogenic capabilities of MSCs from diabetic rats (D-MSCs) versus normal rats (N-MSCs).
- To evaluate the efficacy of D-MSCs in a preclinical model of hindlimb ischemia.
Main Methods:
- Culture-isolation and characterization of MSCs from streptozotocin-induced diabetic and normal rats.
- Assessment of MSC proliferation, osteogenic, and angiogenic differentiation.
- Evaluation of angiogenic factor expression using real-time PCR.
- In vitro assessment of MSC-endothelial cell interactions via tube formation assays.
- In vivo efficacy testing in a rat hindlimb ischemia model using laser Doppler perfusion imaging.
Main Results:
- Diabetic MSCs (D-MSCs) exhibited reduced proliferation rates and aberrant osteogenic and angiogenic differentiation compared to normal MSCs (N-MSCs).
- Lower expression of angiogenic factors was observed in D-MSCs.
- Co-culture of D-MSCs with endothelial cells led to decreased tube formation.
- Transplantation of D-MSCs failed to improve hindlimb ischemia, showing reduced capillary density and angiogenic gene expression in ischemic tissues.
Conclusions:
- Diabetes significantly impairs the proliferation and angiogenic activities of MSCs.
- D-MSCs are ineffective in promoting tissue repair in a hindlimb ischemia model.
- Current strategies using autologous MSCs for cell therapy may require modification or alternative approaches due to diabetes-induced functional deficits.
