Single-Cell Data Links CD271+ to CLI Outcomes
Researchers at Cincinnati Children’s have made a significant discovery that could revolutionize the treatment of critical limb ischemia (CLI). In collaboration with Kanazawa Medical University Hospital in Japan, Oto Inoue, MD, PhD, Juan Sanchez Gurmaches, PhD, and their team have identified a specific type of cell, CD271+, with exceptional potential for promoting blood vessel growth.
CLI causes severe reductions in blood flow to the limbs, often leading to tissue damage and amputation. Despite existing treatments, many patients experience limited relief. Therapeutic angiogenesis, which involves stimulating the growth of new blood vessels, has shown promise as an alternative approach. However, finding the most effective cells for this therapy has been a challenge.
To identify optimal cell populations for angiogenesis, the team used single-cell RNA sequencing (scRNA-seq) to analyze bone marrow, umbilical cord blood and adipose tissue. By focusing on 18,053 lineage-negative cells, they discovered a specific type of cell in the subcutaneous fat, CD271+, with the potential to promote blood vessel formation. This finding offers new hope for CLI patients as it highlights a potentially effective treatment option.
Sanchez Gurmaches explains, “The biggest point here is to try to do regenerative medicine, specifically finding ways to repair damaged tissue. We aim to develop solutions for critical limb ischemia.”
Pinpointing the Best Candidates
Researchers identified three groups of progenitor cells within the CD34+ cells of adipose tissue. Of the 30 markers studied, CD271+ was most strongly linked to cells promoting blood vessel growth, with 98% of CD271+ cells having this ability.
"We found that there is a specific mesenchymal progenitor cell within the subcutaneous fat of people. This cell has a high potential to assist in the regeneration of vasculature," Sanchez Gurmaches says.
In vitro characterization revealed that CD271+ cells exhibited mesenchymal stem cell characteristics, such as enhanced proliferative capacity, compared to CD271- cells. These cells also demonstrated a superior ability to form new blood vessels.
Real Results
CD271+ progenitors demonstrated superior performance in a mouse model of limb ischemia compared to CD271- cells, enhancing blood flow and tissue repair. These CD271+ cells stimulate tissue growth by activating the mTOR pathway, a key process for cell growth and blood vessel formation. The mTOR pathway is activated by CD271 signaling through its co-receptor, TRKB (Tropomyosin receptor kinase B). Blocking mTOR or removing the CD271 protein significantly reduces the ability of these cells to promote blood vessel development.
