Allogeneic transplantation of programmable cells of monocytic origin (PCMO) improves angiogenesis and tissue recovery in critical limb ischemia (CLI): a translational approach

• DOI: 10.1186/s13287-018-0871-8
• Publication Date: 2018-04-27T03:26:32Z
• Authors: Rouven Berndt; Lars Hummitzsch; Katharina Heß; Martin Albrecht; Karina Zitta; Rene Rusch; Beke Sarras; Andreas Bayer; Jochen Cremer; Fred Faendrich; Justus Groß
• Keywords: Critical limb ischemia

Employing growth factor-induced partial reprogramming in vitro, peripheral human blood monocytes can acquire a state of plasticity along with expression various markers pluripotency. These so-called programmable cells monocytic origin (PCMO) hold great promise regenerative therapies. The aim this translational study was to explore and exploit the functional properties PCMO for allogeneic cell transplantation therapy critical limb ischemia (CLI). Using our previously described differentiation protocol, murine were differentiated into PCMO. We examined paracrine secretion pro-angiogenic tissue recovery-associated proteins under hypoxia induction angiogenesis by vitro. Allogeneic performed hind mouse model comparison native placebo group. Moreover, we analyzed retrospectively four healing attempts patients artery disease (PAD; Rutherford classification, stage 5 6). Statistical analysis using one-way ANOVA, Tukey's test or Student's t test, p < 0.05. Cell culture experiments revealed good resilience hypoxia, enhanced release vitro Animal demonstrated significantly SO2 saturation, flow, neoangiogenesis recovery after treatment compared placebo. Finally, first therapeutic application humans increased vascular collaterals improved wound chronic CLI without exaggerated immune response, malignant processes extended infection 12 months. In all minor and/or major amputations lower extremity could be avoided. summary, improve ischemic muscle clinical results provide an effective safe CLI.