Hendrickx, B. (B.)
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- Multipotent adult progenitor cells sustain function of ischemic limbs in mice(American Society for Clinical Investigation, 2008) Zhu, X.H. (Xiao Hong); Chen, W. (W.); Ross, J.J. (John J.); Hendrickx, B. (B.); Peñuelas-Sanchez, I. (Ivan); Uriz, M. (Maialen); Du, F. (F.); Frommer, S.A. (S. A.); Zhang, X. (Xiaoliang); Schroeder, B.A. (Betsy A.); Zhang, Y. (Yi); McCue, J.D. (Jonathan D.); Luttun, A. (Aernout); Jiang, Y. (Y.); Seaborn, M.S. (Meredith S.); Nelson-Holte, M. (Molly); Harris, N.H. (N. H.); Hagenbrock, J. (J.); Prosper-Cardoso, F. (Felipe); Pelacho, B. (Beatriz); Chen, E. (E.); Billiau, A.D. (A.D.); Abizanda-Sarasa, G. (Gloria); Aranguren, X.L. (Xabier L.); Adney, J. (Josuah R.); Verfaillie, C.M. (Catherine M.)Despite progress in cardiovascular research, a cure for peripheral vascular disease has not been found. We compared the vascularization and tissue regeneration potential of murine and human undifferentiated multipotent adult progenitor cells (mMAPC-U and hMAPC-U), murine MAPC-derived vascular progenitors (mMAPC-VP), and unselected murine BM cells (mBMCs) in mice with moderate limb ischemia, reminiscent of intermittent claudication in human patients. mMAPC-U durably restored blood flow and muscle function and stimulated muscle regeneration, by direct and trophic contribution to vascular and skeletal muscle growth. This was in contrast to mBMCs and mMAPC-VP, which did not affect muscle regeneration and provided only limited and transient improvement. Moreover, mBMCs participated in a sustained inflammatory response in the lower limb, associated with progressive deterioration in muscle function. Importantly, mMAPC-U and hMAPC-U also remedied vascular and muscular deficiency in severe limb ischemia, representative of critical limb ischemia in humans. Thus, unlike BMCs or vascular-committed progenitors, undifferentiated multipotent adult progenitor cells offer the potential to durably repair ischemic damage in peripheral vascular disease patients.
- Multipotent Adult Progenitor Cells Support Lymphatic Regeneration at Multiple Anatomical Levels during Wound Healing and Lymphedema(Springer Nature, 2018) Hendrickx, B. (B.); Dheedene, W. (Wouter); Luttun, A. (Aernout); Beerens, M. (Manu); Himmelreich, U. (Uwe); Dresselaers, T. (Tom); Aranguren, X.L. (Xabier L.); Verfaillie, C.M. (Catherine M.)Lymphatic capillary growth is an integral part of wound healing, yet, the combined efectiveness of stem/progenitor cells on lymphatic and blood vascular regeneration in wounds needs further exploration. Stem/progenitor cell transplantation also emerged as an approach to cure lymphedema, a condition caused by lymphatic system defciency. While lymphedema treatment requires lymphatic system restoration from the capillary to the collector level, it remains undetermined whether stem/ progenitor cells support a complex regenerative response across the entire anatomical spectrum of the system. Here, we demonstrate that, although multipotent adult progenitor cells (MAPCs) showed potential to diferentiate down the lymphatic endothelial lineage, they mainly trophically supported lymphatic endothelial cell behaviour in vitro. In vivo, MAPC transplantation supported blood vessel and lymphatic capillary growth in wounds and restored lymph drainage across skin faps by stimulating capillary and pre-collector vessel regeneration. Finally, human MAPCs mediated survival and functional reconnection of transplanted lymph nodes to the host lymphatic network by improving their (lymph) vascular supply and restoring collector vessels. Thus, MAPC transplantation represents a promising remedy for lymphatic system restoration at diferent anatomical levels and hence an appealing treatment for lymphedema. Furthermore, its combined efcacy on lymphatic and blood vascular growth is an important asset for wound healing.