Concise Review: Workshop Review: Understanding and Assessing the Risks of Stem Cell-Based Therapies

Abstract

The field of stem cell therapeutics is moving ever closer to widespread application in the clinic. However, despite the undoubted potential held by these therapies, the balance between risk and benefit remains difficult to predict. As in any new field, a lack of previous application in man and gaps in the underlying science mean that regulators and investigators continue to look for a balance between minimizing potential risk and ensuring therapies are not needlessly kept from patients. Here, we attempt to identify the important safety issues, assessing the current advances in scientific knowledge and how they may translate to clinical therapeutic strategies in the identification and management of these risks. We also investigate the tools and techniques currently available to researchers during preclinical and clinical development of stem cell products, their utility and limitations, and how these tools may be strategically used in the development of these therapies. We conclude that ensuring safety through cutting-edge science and robust assays, coupled with regular and open discussions between regulators and academic/industrial investigators, is likely to prove the most fruitful route to ensuring the safest possible development of new products.

Role of epithelial cells in the pathogenesis and treatment of inflammatory bowel disease

“…As the first therapeutic use of iPS-derived cells was launched last year in Japan for the treatment of macular degeneration [129], application of iPS-derived cells in other organs, such as in the intestine, is highly expected. However, risks and benefits exist in both somatic stem cell based-and pluripotent stem cell-based transplantation therapy [130,131].…”

Cranioplasty with Adipose-Derived Stem Cells, Beta-Tricalcium Phosphate Granules and Supporting Mesh: Six-Year Clinical Follow-Up Results

“…Among the published studies, there is a great variability in, for example, stem cell sources, defect sites and sizes, indications, cell carriers, and use of growth factors that makes it difficult to draw a solid conclusion on stem cell effectiveness in bone tissue engineering 26. Additionally, there has been concern about the safety and efficacy of stem cells in clinical applications 21, 24, 33, 34.…”

“…They are easily retrieved in high numbers from fat tissue and expanded in vitro, which makes them an attractive tool in tissue reconstruction 14, 19, 20. However, scientific evidence in terms of safety and efficacy of ASC use in regenerative medicine is still limited 14, 20, 21, 22, 23, 24.…”

The success of stem cell transplantations and the potential post-transplantation complications may be dependent, among other factors, on the capacity of the recipient and the transplanted cells to repair DNA damage

“…At present, most of the clinically significant types of precursors of differentiated cells (neural progenitors, cardiomyocytes, precursors of osteocytes, chondrocytes, adipocytes and insulin-secreting pancreatic cells, diploid and haploid cells of the spermatocyte lineage, and others) have been successfully derived from murine and human ESC (Phillips 2003, Kroon et al 2008, Elkabetz and Studer 2008, Jukes et al 2010, Easley et al 2012, with the notable exception of human oocyte precursors that proved to be a significant challenge for modern stem cell engineering (Virant-Klun et al 2011, Petkova et al 2014a. In a similar fashion, virtually all types of differentiated cells have already been derived from iPSC , Yoder 2015, Hossain et al 2016,Hu et al 2015 gain, derivation of human germline cells form of iPSC presents a problem, unlike murine iPSC-derived germ cell precursors that were shown to differentiate readily into fully functional spermatozoa and oocytes (Ishii 2014).…”