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.