Sourcing of blood-derived angiogenic cells (BDACs) under serum-free and xeno-free conditions for the treatment of critical limb ischemia
Invited conference paper presented and published in conference proceedings
CUHK Authors
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AbstractBackground 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. Methods As standard BDAC sourcing techniques involve the use of animal-derived serum, we sought to establish a xeno- and/or serum-free protocol. Next, BDACs or MSCs were injected intramuscularly following the ligation of the iliac artery in a murine model. Their ability to enhance revascularization, impair necrosis and modulate inflammatory processes in the affected limb was investigated. Lastly, the secretomes of both cell types were compared to find potential indications for the observed differences in angiogenic potential. Results 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. Conclusions 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. Keywords: Myeloid angiogenic cells, Blood-derived angiogenic cells, Mesenchymal stem cells, Therapeutic angiogenesis, Critical limb ischemia, Xeno/serum free, Revascularization
Acceptance Date26/07/2022
All Author(s) ListWong Christy Wing Tung, Blocki Anna
Name of ConferenceTissue Engineering and Regenerative Medicine International Society – Asia-Pacific Chapter Conference 2022
Start Date of Conference05/10/2022
End Date of Conference08/10/2022
Place of ConferenceJeju ICC
Country/Region of ConferenceSouth Korea
Year2022
LanguagesEnglish-United States
KeywordsAnalysis ; Angiogenesis ; Animal models ; Anti-inflammatory agents ; Antibodies ; Blood-derived angiogenic cells ; Bone marrow ; Critical limb ischemia ; Degeneration ; Drug therapy ; Good Manufacturing Practice ; Growth factors ; Health aspects ; Hemopoiesis ; Inflammation ; Ischemia ; Mesenchymal stem cells ; Mesenchyme ; Myeloid angiogenic cells ; Necrosis ; Pericytes ; Peripheral blood ; Reperfusion ; Revascularization ; Secretome ; serum free ; Stem cell transplantation ; Stem cells ; Therapeutic angiogenesis ; Vascular diseases ; Xeno ; Xeno/serum free