Managing the potential and pitfalls during clinical translation of emerging stem cell therapies

Abstract

We are moving into a new era of stem cell research where many possibilities for treatment of degenerative, chronic and/or fatal diseases and injuries are becoming primed for clinical trial. These reports have led millions of people worldwide to hope that regenerative medicine is about to revolutionise biomedicine: either through transplantation of cells grown in the laboratory, or by finding ways to stimulate a patient's intrinsic stem cells to repair diseased and damaged organs. While major contributions of stem cells to drug discovery, safety and efficacy testing, as well as modelling ‘diseases in a dish’ are also expected, it is the in vivo use of stem cells that has captured the general public's attention. However, public misconceptions of stem cell potential and applications can leave patients vulnerable to the influences of profit driven entities selling unproven treatments without solid scientific basis or appropriate clinical testing or follow up. This review provides a brief history of stem cell clinical translation together with an overview of the properties, potential, and current clinical application of various stem cell types. In doing so it presents a clearer picture of the inherent risks and opportunities associated with stem cell research translation, and thus offers a framework to help realise invested expectations more quickly, safely and effectively.

Pericytes, mesenchymal stem cells and their contributions to tissue repair

“…Several pre-clinical and clinical trials have looked at the therapeutic benefits of systemic infusion of ex vivo isolated and expanded MSCs, but there are problems with the consistency, heterogeneity and delivery of these cells (Main et al, 2014) It is therefore of note that the exposure of rats to chronic hypoxia (3 weeks) increases peripheral blood colony forming unit fibroblasts (CFU-Fs) by almost 15-fold (Rochefort et al, 2006). Subsequently, it was discovered that there is a significant but comparatively low level CFU-F mobilisation after only 2 days of hypoxia that steadily increases over time .…”

“…Adult stem cells of the mesenchymal lineage have been identified in a number of organs, such as the bone marrow, adipose tissue and dental pulp (Main et al, 2014); moreover, there is evidence for an MSC niche associated with the vasculature throughout the body in the form of pericytes (Birbrair et al, 2015). These cell types display remarkable similarities in terms of their marker expression, their ability to self-renew, and their potential to differentiate into multiple mesenchymal cell types such as adipocytes, chondrocytes, osteocytes and myocytes in culture ( Figure 1).…”

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.…”

The large grey area between ‘bona fide’ and ‘rogue’ stem cell interventions — Ethical acceptability and the need to include local variability

“…Joseph Coates pointed out that we lack an adequate ethical framework for relations between institutions, and that raising ethical issues in an institutional context can confuse the issues that cannot be subsumed in terms of ethical guidelines (Coates, 1994). Thus, a narrow focus on a narrow definition of ethics has made medical fees, medical ethics and scientific research fraud central to thinking about 'rogue' experimental stem cell provision (Sipp 2009;McMahon and Thorsteinsdóttir, 2010;Sipp, 2011;Main et al, 2014;Ogbogu et al 2013;Cauldfield, 2015). But generalising and preconceived notions of global inequality, exploitation, and human experimentation on the poor and desperate fail to take into account the variability of their institutional embedding: they are unable to capture the significance of the active roles of patients, scientists and governments that facilitate innovative clinical stem cell applications in low-and middle-income countries (LMICs).…”

“…Various forms and practices of stem cell research and therapy have been criticised, reported and analysed by social scientists and the press (e.g., McMahon and Thorsteinsdóttir, 2010;The Economist, 2002;Sipp, 2011;Main et al, 2014;Ogbogu et al 2013;Cyranoski, 2012). Governments in the US, Hungary, the Netherlands, Germany, Ireland, Belize and elsewhere have closed down clinics that provide 'unauthorised' stem cell therapies, while others fail to stop stem cell providers from charging high fees to administer 'unproven therapies' (Sipp 2009).…”