Sourcing of human peripheral blood-derived myeloid angiogenic cells under xeno-free conditions for the treatment of critical limb ischemia
Authors
Christy Wing Tung Wong, Apurva Sawhney, Yalan Wu, Yi Wah Mak, Xiao Yu Tian, Hon Fai Chan, Anna Blocki
Institution
The Chinese University of Hong Kong
Country
China
Year
2022
Journal
Stem Cell Research and Therapy
Abstract
Critical limb ischemia (CLI) is the most severe form of peripheral artery disease and exhibits a high risk of lower extremity amputations. As even the most promising experimental approaches based on mesenchymal stem cells (MSCs) demonstrated only moderate therapeutic effects, we hypothesized that other cell types with intrinsic roles in angiogenesis may exhibit a stronger therapeutic potential. We have previously established a protocol to source human peripheral blood-derived angiogenic cells (BDACs). These cells promoted revascularization and took perivascular location at sites of angiogenesis, thus resembling hematopoietic pericytes, which were only described in vivo so far. We thus hypothesized that BDACs might have a superior ability to promote revascularization and rescue the affected limb in CLI. From the various commercial media tested, one xeno-free medium enabled the derivation of cells that resembled functional BDACs in comparable numbers. When applied to a murine model of CLI, both cell types enhanced limb reperfusion and reduced necrosis, with BDACs being twice as effective as MSCs. This was also reflected in histological evaluation, where BDAC-treated animals exhibited the least muscle tissue degeneration. The BDAC secretome was enriched in a larger number of proteins with pro-angiogenic and anti-inflammatory properties, suggesting that the combination of those factors may be responsible for the superior therapeutic effect. Functional BDACs can be sourced under xeno-free conditions paving the way for their safe clinical application. Since BDACs are derived from an easily accessible and renewable tissue, can be sourced in clinically relevant numbers and time frame and exceeded traditional MSCs in their therapeutic potential, they may represent an advantageous cell type for the treatment of CLI and other ischemic diseases.
Product use
Sourcing of human peripheral blood-derived angiogenic cells (BDACs) in xeno-free condition with CnT-PR-MSC-XF