Stem cell therapy: an exercise in patience and prudence

Abstract

In recent times, the epigenetic study of pluripotency based on cellular reprogramming techniques led to the creation of induced pluripotent stem cells. It has come to represent the forefront of a new wave of alternative therapeutic approaches in the field of stem cell therapy. Progress in drug development has saved countless lives, but there are numerous intractable diseases where curative treatment cannot be achieved through pharmacological intervention alone. Consequently, there has been an unfortunate rise in incidences of organ failures, degenerative disorders and cancers, hence novel therapeutic interventions are required. Stem cells have unique self-renewal and multilineage differentiation capabilities that could be harnessed for therapeutic purposes. Although a number of mature differentiated cells have been characterized in vitro, few have been demonstrated to function in a physiologically relevant context. Despite fervent levels of enthusiasm in the field, the reality is that other than the employment of haematopoietic stem cells, many other therapies have yet to be thoroughly proven for their therapeutic benefit and safety in application. This review shall focus on a discussion regarding the current status of stem cell therapy, the issues surrounding it and its future prospects with a general background on the regulatory networks underlying pluripotency.

Figure 1.

A pyramidal hierarchy of cell potency. Sitting atop the pyramid (red), cells of the morula are the most potent cells that can differentiate into all tissue types. ESCs and iPSCs occupy the next level, as they cannot differentiate into the placenta (orange). Tissue resident stem cells (HSCs, NSCs, EpSCs) can differentiate into multiple cell types restricted to that lineage (yellow). At the base are cells with more limited differentiation potential (CMP, CLP) usually committed progenitors (light green). TOTI, totipotent; PLURI, pluripotent; MULTI, multipotent; OLIGO, oligopotent; ESC, embryonic stem cell; iPSC, induced pluripotent stem cell; HSC, haematopoietic stem cell; NSC, neural stem cell; EpSC, epithelial stem cell; CMP, common myeloid progenitor; CLP, common lymphoid progenitor.

Figure 2.

Derivation and establishment of embryonic stem cells (ESCs). Zygotes are maintained until reaching the morula or blastocyst stages of development. Cells from the intra cellular mass (ICM) are extracted and maintained in vitro on a feeder layer of cells.

Figure 3.

Generation and applications of induced pluripotent stem cells (iPSCs). A somatic cell source is isolated from the patient. Pluripotency-associated genes are delivered to reprogramme the cell. Applications of iPSCs include cell therapy and studies of pathogenesis.

Figure 4.

A comparison of stem cell characteristics and major categories of interventional trials. (a) Table comparing stem cell characteristics between embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and somatic stem cells (SSCs). (b) Bar graph comparing the relative numbers of open trials of the major stem cell categories (www.clinicaltrials.gov and modified from [43]). MSC, mesenchymal stem cell.