Advantages of Regenerative Medicine
Novel Treatment for Diseases and Injuries: The long term goal of regenerative medicine is to provide permanent cures for ailments by generating functional cells, tissues and organs that can be used to replace, repair or improve lost, damaged and diseased tissue. Currently most diseases are treated with medications, surgery, and other pharmacological therapies. Regenerative medicine could revolutionize the medical industry and how we treat diseases. Having the ability to regenerate organs opens the door to increase longevity and reduce the effects of aging by replacing older malfunctioning organs with healthier functioning organs. Although this level of regenerative medicine may be several years or decades away from becoming a standard practice, successful engineering and transplantation of healthy organs are currently being performed. In a study by Atala et al (2006), urothelial and muscle cells biopsied from patients with end-stage bladder disease were expanded and seeded on to a scaffold to generate bladder constructs. These constructs were then used to reconstruct a healthy bladder. The bladders were implanted into the patients and returned normal bowel function to the patients.
Personalized Medicine and Gene Therapy: Regenerative medicine offers the opportunity to use cells as vehicles for gene therapy and/or for the correction of gene mutations by replacing mutants with corrected genes. In theory, autologous cells (cells that were obtained from the same individual) from a patient with a genetic disease would be harvested and reprogrammed into iPSCs. The cells would then undergo gene modification using one of several methods such as zinc finger nucleases, TAL effector nucleases, or the safer and more effective clustered regulatory interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) system. The gene-corrected cells would then be expanded in vitro, differentiated into the target cell lineage, and administered to the patient by injection or on a biodegradable scaffold (Angelos & Kaufman, 2015). Evidence of the effectiveness of this regenerative strategy was demonstrated in a study by Xie et al in 2014. In their study, they used CRISPR/Cas9 to repair iPSCs derived from patients with β-thalassemia, a genetic blood disorder resulting in abnormal hemoglobin due to mutations in the HBB locus. Implantation of gene-corrected differentiated cells resulted in production of cells expressing the normal form of HBB.
Reduces Risk of Rejection: Another potential benefit of regenerative medicine is that it removes the risk of organ transplant rejection. The ability to harvest and expand cells from patient ASCs to generate healthy cells would significantly decrease the risk of an immunogenic response to the implant, thus removing the need to treat patients with immunosuppressive drugs and decreasing their risk of infection.
Improves Disease Models for Biomedical Research: Regenerative medicine and stem cell technology not only lead to advances in the clinic, but in the lab as well. The ability to development functional tissues and organs outside the body would provide accurate models to research the effect of disease and other harmful factors on the body. It also provides an opportunity to test the efficacy and safety on potential therapeutics on human models prior to clinical trials. Providing vital information prior to spending a considerable amount of funds and time on a drug of unknown efficacy. Preclinical testing with human tissues may also reduce the risk to participants in a clinical trial for a potentially harmful therapy.
Challenges of Regenerative Medicine
Stem Cell Expansion: Despite the advances made in implementing stem cells, there are still several obstacles to its use in the clinic. A major obstacle in regenerative medicine is the need for a large amount of cells. The typical solution has been to generate cells from ASCs, since they are readily available and believed to be safe. However, obtaining these cells has been a challenge. Research efforts are striving to develop methods to obtain greater numbers of ASCs from patients and to enhance expansion of cultured stem cells. While there has been some success in enhancing expansion of hematopoietic stem cells (HSCs) in vitro with cytokines, the cells generated have reduced proliferative capacity, limiting their use for tissue regeneration. Expanding stem cells in environments that mimic the stem cell niche has shown some promise. For example, HSCs cultured with mesenchymal stem cells in a 3D environment results in more stem-like cells than culturing HSCs in a 2D environment. Skeletal muscle stem cells grown on a substrate similar to muscles also improves cell expansion in culture as well as improves stem cell proliferative capacity. More research is needed to optimize cell expansion.
Immunological Tolerance: Another concern is the lack of immunological tolerance to cell transplants. Several studies have found that mature cells derived from ESCs can elicit an immune response (Swijnenburg, et al., 2005; Swijnenburg, et al., 2008). There is also evidence that proteins generated from gene-corrected autologous cells can also be immunogenic as well (Witmer & Young, 2013). While treatment with immunosuppressive medication can alleviate this issue, it can also increase the risk to the patient by increasing their susceptibility to infection. Other solutions include co-implantation with anti-inflammatory T-regulatory or mesenchymal stromal cells to reduce immune response to the implanted stem cells.
Streamlining Production: Another major obstacle is streamlining the therapeutic use of stem cells. Current protocols to maintain, expand, or in the case of iPSCs, produce stem cells are extremely complex and would require a significant amount of regulation and oversight to generate reproducible products. These products would also have to undergo extensive testing before receiving FDA approval.
Other Research Obstacles: There are several questions that need to be answered before regenerative medicine can truly be implemented. This includes developing the technology to robustly differentiate stem cells into cells of a specific lineage in a controlled manner; determining which cell stage, stem cell, or precursor is the best to use for specific therapeutic purposes; developmenting/ identificating biomarkers to adequately identify pluripotent cells; understanding the influence of the host tissue environment on cell behavior; developing biomaterials to enhance cell survival, growth and differentiation, reduction of genetic changes during cell culture; and developing an effective cell delivery system (Polak, 2010).
