Billiau, A.D. (A.D.)

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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.