Challenges in the clinical development of stem cell therapy

Abstract

The idea behind cell therapy is not new; it was proposed many years ago. However, the significant research activities in the regenerative medicine field started in the 1970s. Over the last decade the advances in the understanding of stem cell biology have made the prospect of tissue regeneration a potential clinical reality. A potential strategy to replace, repair and restore the function of damaged tissues or organs is stem cell transplantation. Cell therapeutics may perform better than current treatments such as medical devices, recombinant proteins and chemical compounds. Despite advances made in the past few years and the accumulating body of evidence supporting the contribution of stem cells in tissue regeneration, many questions regarding their clinical application need to be addressed [1]. Processes to produce cell-based therapeutics are not standardized yet and are highly variable. The critical challenge for translating stem cell therapy into the clinic is to deliver safe, effective and affordable therapies to patients. Types of cells and routes of administration for specific clinical scenarios would need to be determined in order to maximize potential therapeutic benefit. Furthermore, it is necessary to determine the quantity of cells needed for transplantation to achieve best possible therapeutic effect. The type of patients that would benefit from this treatment must be determined. The desirable features of stem cells for therapy include rapid expansion in vitro and minimal immunogenicity and regenerative properties when transplanted into injured organs. Possible candidate cells to be used include various stem cells such as adult stem cells, embryonic stem (ES) cells and recently generated pluripotent stem cells (iPS) [2] that closely resemble ES cells. ES cells have an unlimited self-renewal ability and the capacity to differentiate into any specialized cell type, therefore, could represent an unlimited cell source for tissue regeneration. However, research on these cells has been hampered or banned in some countries because of the ethical concerns about destroying human embryos to obtain them. Another major limiting factor for their usefulness in clinical therapy lies in their risk of uncontrolled growth and potential danger of teratoma formation and immunological intolerance [3,4]. In spite of this, the US biotechnology company Geron have performed the first US FDA-approved clinical trial using ES-derived glial oligodendrocytes in patients with acute spinal cord injury. The results have not been published yet, but the trial is aiming to elucidate whether ES cells are safe to use in patients and also if they improve patients’ sensation in the trunk or legs. Using iPS cells can bypass ethical and immunological issues and may offer the possibility of developing patient-specific cell therapeutics. However, the use of oncogenic viruses to make the iPS is considered unsafe for clinical applications and there is a possibility of tumour genesis. Improved induction methods more suitable for clinical use are under development [5]. Moreover, patient-specific therapy is associated with high cost and regulatory issues. Currently,