The Niche

Reader response: Stem cell culture should consider not just dimensions but tissues

Our recent article, Thinking in three dimensions: some stem cell researchers think conventional culture falls flat, brought this response from Xiao-Dong Chen of the University of Texas Health Science Center:

There is no doubt that the use of 3-dimensional (3D) matrix for culturing mesenchymal stem cells (MSCs) is more closely relevant to physiological situation as compared to 2D culture systems. However, more important it is time to think in “tissue-specific 3D matrix” rather than 3D matrix that is simply prepared from a single component of synthetic products or purified matrix proteins such as type I collagen or fibronectin.

MSCs can differentiate into many distinct cell lineages. The direction of MSC differentiation is controlled by tissue-specific microenvironment or niche that is mainly constituted by extracellular matrix (ECM) proteins associated with growth factors. Indeed, it is very doubtful that the intricate and highly ordered nature of the ECM could be reproduced with synthetic or purified components. To attempt to reconstitute the MSC niche in vitro, we prepared an ECM made by bone marrow stromal cells. This marrow stromal cell-derived ECM dramatically promotes the replication of MSCs and facilitates the retention of their multipotentiality (Journal of Bone and Mineral Research 2007, 22:1943-1956). One potential mechanism for the retention of MSC properties may be associated with the ability of the ECM to sequester most endogenously produced growth factors that control MSC replication and differentiation. It is worth investigating whether the stromal cell-derived ECM is unique in its ability to preserve MSC properties by comparing to ECM made by fibroblasts from different tissues such as skin, fat and muscle. Establishment of a unique scaffold built by 3D synthetic materials coated with tissue-specific ECM proteins and deposited with an appropriated combination of growth factors will facilitate control of the fate of MSCs for the therapeutic applications.

Xiao-Dong Chen, MD, PhD

Associate Professor

Department of Restorative Dentistry

University of Texas Health Science Center

7703 Floyd Curl Dr. MC-7890

San Antonio, TX 78229-3900

chenx4 [ at ] uthscsa.edu

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