Regenerative medicine is the restoration of normal function to diseased, injured or lost tissues using therapies consisting of living human cells, tissues, or organs with or without specialized materials. The concept of using tissues to replace damaged tissues has been around for centuries. However, the field of regenerative medicine as it currently stands began to develop following the discovery of human stem cells or more specifically embryonic stem cells, in the late 1990s.
Stem cells are cells capable of developing or differentiating into more specialized cells such as heart, lung, skin, pancreas and many more. Because of their capacity to generate cells from multiple lineages, researchers have begun to investigate their potential for regenerative medicine. In theory, stem cells could be harvested from a patient and used to generate many different types of healthy tissue. The tissue would then be implanted in the patient to replace the damaged or diseased tissues. Stem cells and bio-materials are the corner stone of regenerative medicine, below is a breif overview of both.
Stem Cells
In the human body there are two categories of stem cells: adult stem cells (ASCs) and embryonic stem cells (ESCs). ASCs are located in every tissue of the human body and give rise to new cells throughout adulthood to maintain and repair their tissue of origin. ACSs are multipotent, meaning that they are able to develop into more than one cell type (typically belonging to the lineage of the tissue of origin).
There are several obstacles to using ACS stem cells in this manner. A major concern is the limited accessibility and low frequency of stem cells. For example, in bone marrow cells, there is approximately 1 stem cell for every 100,000 bone marrow cells. Another limitation is the limited differentiation potential of ASCs, limiting the tissue types that can be generated. ASCs can also only differentiate a finite number of times and are susceptible to mutations over that time. ASCs are also difficult to grow outside of the body, making regular clinical use less practical.
Compared to ASCs, embryonic stem cells have more advantages when it comes to regenerative medicine. ESCs are pluripotent, meaning they are capable of differentiating into any cell type in the body. ESCs can also proliferate for an extended period of time. However, a major drawback that makes ESCs impractical for clinical use is that they can only be obtained from early stage embryos, which raises many ethical issues. Another disadvantage to using ESCs compared to ASCs is that the cells would be allogenic, or have a different origin than the patient, which introduces immunological concerns and lessens their therapeutic potential.
In 2006, Takashi and Yamanaka provided an alternative to adult and embryonic stem cells by generating induced pluripotent stem cells (iPSCs) from skin cells using four transcription factors: Oct 4, Sox2, Myc and Klf4 (Takahashi & Yamanaka, 2006; Takahashi, et al., 2007). This breakthrough provided a stem cell alternative that lacked the ethical concerns and limited potential associated with other stem cells used in regenerative medicine.
There were initial concerns that the use of oncogenic viruses to generate iPSCs made it an unrealistic option for clinical use. Since then, several virus-free methods of iPSC production have been developed (Clarke & van der Kooy, 2009). However, there are still some issues related to using iPSCs for regenerative medicine purposes. Multiple studies have found that iPSC differentiation potential is significantly lower than that of ESCs. iPSCs also frequently undergo cell death by apoptosis and senescence, which is failure to divide.
Biomaterials
Biomaterials are another component of regenerative medicine. Biomaterials are natural or synthetic substances that interact with biological systems for medical purposes to improve or replace a natural function. These materials can be used to support cell growth, survival, and to direct cell behavior. Some biomaterials are even capable of generating a cellular response within the body, making the use of live cells unnecessary. Optimal biomaterials are biocompatible, biodegradable, implantable, resilient, and porous to allow for the transfer of nutrients and waste and tissue growth.
