Single cell transcriptomics identifies adipose tissue CD271+ progenitors for enhanced angiogenesis in limb ischemia

Area of Science:

• Regenerative Medicine
• Stem Cell Biology
• Vascular Biology

Background:

• Mesenchymal stem/stromal cell grafts show limited success in preventing amputation for critical limb ischemia.
• Identifying potent pro-angiogenic cell populations is crucial for advancing cell-based therapies.

Approach:

• Utilized single-cell transcriptomic analysis of human tissues to identify distinct stem cell populations.
• Characterized the angiogenic potential of CD271 positive progenitors from subcutaneous adipose tissue (AT).
• Evaluated the in vivo therapeutic efficacy in a xenograft model of limb ischemia.

Key Points:

• Adipose tissue CD271 positive progenitors exhibit a superior pro-angiogenic gene profile compared to other stem cell sources.
• These progenitors demonstrate robust in vivo angiogenic capacity, including long-term engraftment and enhanced tissue regeneration.
• Angiogenic function is dependent on CD271 and mTOR signaling, and is significantly reduced in insulin-resistant donors.

Conclusions:

• CD271 positive progenitors from adipose tissue represent a highly effective cell source for therapeutic angiogenesis in limb ischemia.
• The study highlights the utility of single-cell transcriptomics for identifying optimal cell grafts for regenerative therapies.
• Impaired progenitor function in insulin resistance presents a challenge for cell therapy efficacy in specific patient populations.