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

Area of Science:

• Regenerative Medicine
• Vascular Biology
• Stem Cell Biology

Background:

• Mesenchymal stem/stromal cell grafts show controversial efficacy in preventing amputation for critical limb ischemia.
• Identifying potent cell populations for therapeutic angiogenesis is crucial.

Purpose of the Study:

• To identify specific progenitor cells from adipose tissue with superior pro-angiogenic potential for treating critical limb ischemia.
• To investigate the in vivo efficacy and underlying mechanisms of these identified progenitors.

Main Methods:

• Single-cell transcriptomic analysis of human tissues to profile stem cell populations.
• In vivo xenograft model of limb ischemia to assess angiogenic capacity and therapeutic effects.
• Functional assays to determine the role of CD271 and mTOR signaling.

Main Results:

• CD271+ progenitors from subcutaneous adipose tissue exhibit a distinct pro-angiogenic gene profile.
• These progenitors demonstrate superior in vivo angiogenic capacity, long-term engraftment, and enhanced tissue regeneration compared to conventional grafts.
• Angiogenic potential is dependent on CD271 and mTOR signaling, and is reduced in insulin-resistant individuals.

Conclusions:

• Adipose tissue-derived CD271+ progenitors represent a promising cell source for therapeutic angiogenesis in critical limb ischemia.
• Single-cell transcriptomics is a valuable strategy for identifying optimal cell grafts for regenerative medicine.
• Reduced progenitor efficacy in insulin resistance highlights potential challenges and therapeutic targets.