Nature or Nurture

Mesenchymal stem cells (MSCs) have been and remain very popular among cell therapists and tissue engineers, as shown by the use thereof in over 500 clinical trials. This success is justified by the diverse positive contributions exerted by MSCs toward tissue (re)generation and repair as tissue progenitors, proangiogenic cells, immunosuppressors, and supportive cells for lineage-committed stem cells. MSCs are, in addition, remarkably easy to isolate since MSC extraction is a mere primary culture of unselected dissociated cells. While convenient, indirect selection in long-term culture has long obscured the native biologic identity and tissue distribution of mesenchymal stem cells. It is only in recent years that perivascular cells – pericytes and cells of the tunica adventitia – have been identified as natural contributors of MSCs. Perivascular cells purified to homogeneity by flow cytometry show outstanding repair ability in bone and other tissues. Herein, we briefly review the medical utilization of conventional, culture-derived MSCs and discuss whether these should be, in some indications, advantageously replaced by their prospectively selected perivascular ancestors.