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16 Mesenchymal Stem Cells of Human Adult Bone Marrow

Mark F. Pittenger, Daniel R. Marshak


We define stem cells broadly as those cells that give rise to progeny with more than one differentiated phenotype and that may be greatly expanded in an undifferentiated form. This differs from a “progenitor cell,” which gives rise to a single cell lineage only. Human mesenchymal stem cells (hMSCs) are isolated from bone marrow and expanded ex vivo. Flow cytometry using many different surface markers has demonstrated the expanded population to be >98% homogeneous and in defined in vitro assays these cells readily differentiate to multiple connective tissue lineages, including osteoblasts, chondrocytes, and adipocytes (Fig. 1) (Pittenger et al. 1999). In vivo implantation of these cells at orthotopic sites will also yield tissues in these lineages. Additionally, cultured hMSCs either produce, or can be induced to produce, cytokines for support of hematopoietic cells (Majumdar et al. 1998; Cheng et al. 2000). Cocultures of the MSCs with hematopoietic stem cells (HSCs) demonstrated that hMSCs or adipogenic hMSCs can support the in vitro maintenance, and even expansion, of HSCs, suggesting hMSCs serve as functional stroma (Thiede et al. 2000). In addition, conditions that produce myogenic differentiation of rat MSCs have been reported (Saito et al. 1995), and hMSCs show similar behavior but perhaps less efficiently. MSCs with similar potential have been isolated from other species as well, and those isolated from rabbits differentiated to tenocytes to produce a suitable replacement for severed tendon with excellent biomechanical stability (Young et al. 1998). The rabbit MSCs were also shown to form suitable cartilaginous grafts...

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