Mesenchymal Stem Cells - Interest Group
Directed Differentiation of  MSCs towards Intra-Mesenchymal

Mesenchymal stem cells (MSCs) are multipotent stem cells that can differentiate
into a variety of cell lineages.  Cell types that MSCs are capable of differentiating
into in vitro or in vivo include:

  • Osteoblasts
  • Chondrocytes
  • Myocytes
  • Adipocytes

Ever since scientists Ernest McCulloch and James Till first revealed the clonal
nature of marrow-derived mesenchymal cells in the 1960s, it has been
understood that MSCs are characterized by plasticity and their fate can be
determined by environmental cues.   They discovered that culturing marrow
stromal cells in the presence of osteogenic stimuli such as ascorbic acid, inorganic
phosphate, and dexamethasone could promote their differentiation into
osteoblasts. Alternatively, the addition of transforming growth factor-beta (TGF-b)
could induce chondrogenic markers. Myocyte and adipocyte differentiation can be
similarly induced.

More recently, it has also been demonstrated that MSCs have the potential to
differentiate into beta-pancreatic islets cells . Chen et al., of the Union Hospital of
Huazhong University in China, explored the possibility that marrow mesenchymal
stem cells could have the capacity to differentiate in vitro into functional islet-like
cells, and therefore, be used for diabetes therapeutic application.  His research
team found that when Rat MSCs were isolated from Wistar rats and cultured,
passaged MSCs could indeed be induced to differentiate into typical islet-like
clustered cells. Insulin mRNA and protein expressions were positive in
differentiated cells, and nestin could be detected in pre-differentiated cells.
Furthermore, insulin excreted from differentiated MSCs was much higher than
that from pre-differentiated, and injecting the differentiated MSCs into diabetic
rats supported down-regulation of glucose levels.  As such, MSC-derived islet-like
functional cells may ultimately play an important role in diabetes therapy by islet
differentiation and transplantation.  

Directed differentiation of autologous mesenchymal stem cells (MSCs) towards
intra-mesenchymal lineages is an application that involves working toward the
identification of pharmacological and molecular pathways driving MSC
differentiation toward mesenchymal derivatives in vitro. Its goal is to gradually
elucidate the molecular mechanisms governing MSC differentiation in vivo.  In
particular, there is a need to develop reliable methods for directing the
differentiation of human mesenchymal stem cells (hMSC) for use in regenerative
medicine applications. Most research in this area is focused on embedding
mesenchymal cells in defined protein microenvironment and tracking directed
differentiation through cell morphology, gene express, and cell activity.