The role of biomaterials in stem cell-based regenerative medicine

Despite their vast therapeutic potential in such areas as cell therapy and tissue engineering, stem cells have yet to live up to their original hype and demonstrate widespread clinical success.

stem cell

There is only one FDA-approved stem cell treatment, that being the use of blood-forming stem cells derived from cord blood, which have been used for the treatment of leukaemia for decades. Despite the recent rapid advances within the field of stem cell research, and an ever-growing population of researchers in academia, biotech, and the pharmaceutical industry focused on the development of stem cell-based treatments for a range of conditions, there has been a limited progression of such research from bench to bedside.

The lack of success in translation of stem cell technologies to clinical applications can be attributed to a range of issues, from the well-documented ethical, legal, and social controversies which surround the use of certain stem cells, to practical obstacles such as challenges in obtaining a sufficient quantity of cells required for clinical applications, and issues in achieving efficient and uniform differentiation of stem cells into functional derivatives for the regeneration of damaged tissues. As our understanding of stem cells and their interaction with their environment develops, it has become apparent that the use of biomaterials to improve stem cell cultures and control stem cell behaviour will be vital for cellular therapy and tissue regeneration.

The combination of an aging population, demand for a higher quality of life, and the lack of any effective therapies or cures for the treatment of spinal cord or traumatic brain injuries, or neurodegenerative diseases like Alzheimer’s disease and Parkinson’s disease, has led to the emergence of regenerative medicine and tissue engineering as a solution. With their ability to self-renew and differentiate into specialised cell types, the interest in utilising stem cells for the regeneration of damaged / lost tissue and organs has intensified. There are three types of stem cells; embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are capable of unlimited self-renewal and can differentiate into any of the over 200 types of cells in the body. The third, adult stem cells, which include mesenchymal stem cells (MSCs) are isolated from various sources, such as bone marrow and adipose tissues, and are multipotent ie, they differentiate into only limited cell types. Whilst ESCs and iPSCs can pose issues due to uncontrolled differentiation and tumorigenicity, and the ethical concerns surrounding their use, adult stem cells like MSCs are not plagued with such concerns. Based on this and their relative ease of culture, MSCs are one of the most widely studied stem cells in regenerative medicine.

MSCs exist in almost all types of tissues. They possess a multilineage potential, with their capacity to self-renew and differentiate into specialised cell types being dependant on their source of isolation. Previously it has been demonstrated that they are able to differentiate into adipocytes, chondrocytes and osteocytes, myoblasts, cardiomyocytes and neurons in vitro and in vivo. In addition to their differentiation capabilities, lack of ethical concerns, and no reported tumorigenicity, the wide availability of autologous sources and emerging evidence that they are immunosuppressive make MSCs even more attractive candidates for regenerative medicine applications. 

For the successful incorporation of MSCs into cell therapy and tissue engineering applications, a thorough understanding of the factors which influence their behaviour is vital. Their fate decisions are driven by various instructive factors from their immediate vicinity or microenvironment. These biochemical and biophysical cues play a key role in determining the efficacy of MSC differentiation and thus their contribution to the repair process.  The ability to tailor such cues and incorporate them into the design of specific 3-D microenvironments would allow the direction of stem cell fate and potentially optimise and facilitate tissue repair / regeneration. It is in this context, that an understanding of materials science and design becomes important, in allowing the creation of biomaterials that possess the optimal biochemical and mechanical properties required to manipulate the stem cells for specific therapeutic applications. Indeed, it is believed by many that due to low proliferation rates and limited lifespan, MSCs alone would not be able to meet the demands of tissue engineering / regenerative therapies and that strategies which exploit the interaction of MSCs and biomaterials will be vital in translating this stem cell research to the clinic.

It is known that the most significant element in regulating MSC fate is the ECM. Stem cells are attached to the ECM via adhesion molecules, and cell-ECM interactions play a key role not only in cell adhesion, but cell morphology, cell-cell interactions, and differentiation. This interaction between stem cells and biomaterials is the key basis for influencing stem cell properties in vitro or in vivo. As such, within tissue engineering, biomaterials should be designed to mimic the biological and physical properties of the microenvironment of native ECM found in tissues, thereby attempting to recreate the native niche of stem cells or MSCs derived from particular sources.

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