HEMATOPOIETIC STEM CELLS VII Perivascular Multipotent Progenitor Cells in Human Organs Mihaela Crisan, a Chien-Wen Chen, a Mirko Corselli, a Gabriella Andriolo, b Lorenza Lazzari, b and Bruno P´ eault a,c a Stem Cell Research Center, Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA b Cell Factory, Department of Regenerative Medicine, Fondazione Ospedale Maggiore Policlinico, Milan, Italy c McGowan Institute for Regenerative Medicine, Pittsburgh, Pennsylvania, USA We have identified vascular pericytes in multiple human organs on expression of CD146, NG2, PDGF-Rβ, and mesenchymal stem cell markers (CD44, CD73, CD90, CD105) and absence of blood, endothelial, and myogenic cell markers. Pericytes purified from all tissues were myogenic in culture and in vivo, sustained long-term culture during which they expressed markers of mesenchymal stem cells, and exhibited, at the clonal level, osteogenic, chondrogenic, and adipogenic potentials. These results suggest that human capillary and microvessel walls all over the organism harbor a reserve of progenitor cells that are at the origin of the elusive mesenchymal stem cells, so far identified only retrospectively in primary tissue cultures. Key words: pericyte; mesenchymal stem cell Introduction The vertebrate embryo is built from multi- lineage stem cells that become gradually segre- gated, in the course of development, into tissue- specific progenitor cells. Such committed stem cells persist in adult organs, in which they re- generate tissues lost to disease, trauma, or aging. Yet, with the exception of the hematopoietic system, no human organ can be routinely re- generated in the clinic with tissue-specific stem cells. Although the presence of such committed progenitor cells has been documented in most tissues, these are rare, of generally unknown phenotype, and therefore inaccessible as pure populations of clinically relevant size. Hence the interest elicited by cells endowed with broad developmental potential, which were initially extracted from adult bone marrow cultures as Address for correspondence: Bruno P´ eault, UCLA - Orthopaedic Hospital Research Center, 615 Charles E. Young Dr. South, Los Angeles, CA 90095-7358. Voice: 310-794-1339; fax: 310-825-5409. bpeault@mednet.ucla.edu. mesenchymal stem cells (MSC). 1,2 MSC have properties compatible with utilization in regen- erative medicine. Principally, these cells can be cultured over the long term with no alteration of their developmental potential; MSC also have a marked immunosuppressive function, 3 suggesting their superior transplantability in an allogeneic setting. Moreover, MSC-like cells are present in multiple tissues, including the most accessible ones such as the placenta, umbilical cord, and adult fat. 4 Bone marrow MSC and their counterparts in other organs have been, however, identi- fied only indirectly, in long-term cultures of the tissue of origin, giving no clue as to the na- tive distribution and anatomic localization of these stem cells. We have addressed the identity of native multilineage stem cells within mul- tiple fetal and adult human tissues and doc- umented the widespread presence of MSC- like cells closely associated with the walls of blood vessels. We have identified, marked, and purified to homogeneity pericytes that closely surround endothelial cells in small blood Hematopoietic Stem Cells VII: Ann. N.Y. Acad. Sci. 1176: 118–123 (2009). doi: 10.1111/j.1749-6632.2009.04967.x c  2009 New York Academy of Sciences. 118