History

The concept that post-natal tissues self-renew, and do so by means of a stem/progenitor cell, is not a new one, being based on observations made around 1900, primarily in the field of hematology. While this concept was originally thought to apply to tissues with a high rate of turnover (blood, the gastrointestinal tract, epidermis), studies over the past few decades have demonstrated that virtually all tissues, including connective tissues, have the ability to self-renew, albeit at different rates, depending on the demands imposed upon them [1]. Methods to establish cell cultures in vitro were first attempted in the late 1800s and early 1900s by a number of investigators, namely Bernard, Roux, Harrison, and others [2], but it is Alexis Carrel who is credited with the methodology employed to establish and maintain connective tissue cells in vitro [3]. With subsequent refinements in the following years, connective tissue cell cultures rapidly became an essential tool in cell physiology and molecular biology. Perhaps the first real evidence of stem/progenitor cells within a population of connective tissue cells emerged in the late 1960s, when Alexander Friedenstein and co-workers isolated clones of rapidly adherent bone marrow stromal cells (BMSCs), derived from a single cell, a colony-forming unit-fibroblast (CFU-F). Approximately 10%–20% of single CFU-F-derived strains had the ability to form bone, hematopoiesis-supportive stroma, and marrow adipocytes upon in-vivo transplantation in open systems, and cartilage as well in closed systems. Friedenstein and his collaborator, Maureen Owen, later called these cells “multipotent bone marrow stromal stem cells” [4, 5]; more recently, the term “skeletal stem cell” has been coined [6].

Connective tissue stem/progenitor cells in tissue engineering and regenerative medicine

Over the last several decades, putative stem/progenitor cells have been isolated from a long list of connective tissues. These cells have been collectively termed “mesenchymal stem cells” or more recently “mesenchymal stromal cells” (“MSCs”), because of their adherence to tissue culture plastic, fibroblastic morphology, and expression of cell surface markers [7]. How similar or dissimilar “MSCs” are from different connective tissues, and whether they are true stem/progenitor cells, is not well known [8]. Nonetheless, these populations may be useful in the reconstruction of connective tissues.