5. Challenge and future prospects
Both MSC therapy and EPC therapy are promising due to their outstanding effectiveness and low toxicity, and the effects of MSC therapy and EPC therapy also have been verified in many diseases thus far. However, because of our limited understanding of cell differentiation regulation, we poorly predict the further development of transplanted MSCs and EPCs. Except for ethical issues, challenges mainly include the following three aspects (Luo et al., 2013).(1) Low abundance: Human stem cells are derived from human tissue such as bone marrow, adipose, amniotic fluid, and umbilical cord blood, and therefore, due to the sparse volume of tissue, obtaining vast numbers of stem cells will become an insurmountable hurdle. However, the emergence of IPSC technology may solve this problem. There exist many methods to induce somatic cells, including virus, vector, mRNA, protein, small molecules, and miRNA(Ichida et al., 2009; Moradi, Braun, & Baharvand, 2018; Moradi et al., 2017; Zhu et al., 2010). Unfortunately, the most efficient method is accompanied by the highest danger. Therefore, further study is necessary to obtain a method that will balance safety and efficiency(Okita, Nakagawa, Hyenjong, Ichisaka, & Yamanaka, 2008; Stadtfeld, Nagaya, Utikal, Weir, & Hochedlinger, 2008; Woltjen et al., 2009). (2) Genomic insertion and incomplete reprogramming: Gene editing technology and inducing pluripotent stem cell technology require carriers to transfect transcription factors, while under some rare situations, exogenous cDNA can be inserted into the host’s chromosomal DNA. However, due to undetectable mutations and unknown genesis positions, nobody knows what will happen if genomic insertion occurs or if incomplete reprogrammed stem cells replicate and differentiate in a patients’ body(Selvaraj, Plane, Williams, & Deng, 2010). (3) Tumorigenicity: all stem cells probably develop to tumor cells after replication and differentiation for a long period of time. This phenomenon has been verified by many studies, because all stem cell transplantations finally develop to a tumor. Additionally, the process of inducing pluripotent stem cell technology also increases the tumorigenicity of pluripotent stem cells, because the transcription factor Myc is a protooncogene that will lead to the occurrence of tumors. Fortunately, Yamanaka reported that a new technology can create IPSCs without Myc(Aguilar-Gallardo, Cristóbal, Simón, & Carlos, 2013), and although its efficiency is much lower, this provides us with a satisfactory idea for safety technology(Marión et al., 2009).
The future of stem cell therapy is promising. In the past 2 decades, stem cell therapy has been applied to numerous fields, including interstitial pulmonary fibrosis, limbal stem cell deficiency, progressive multiple sclerosis, diabetes, myocardial infarction, and neurodegenerative disease. Different from other conventional drug therapies for pathogenesis, stem cell therapy has obvious advantages because it can directly involve in cell regeneration. Therefore, stem cells provide a new therapy that conventional drug therapy cannot achieve.
A large number of animal studies and clinical trials show that significant improvement results from combined therapy as compared with traditional drug therapy. However, stem cell therapy is not a mature therapy because we know little about its potential mechanism. Therefore, in the next stage of research, we should first design new experiments to explore the detailed mechanisms of stem cell therapy, and second, we should summarize clinical experiences to provide a suitable therapy course. Last but not least, we should discuss the ethical issues regarding allotransplantation. If we can obtain insight into the specific mechanism of stem cell therapy and achieve a feasible consensus regarding allotransplantation, then the applications for stem cell therapy will greatly expand.