Regulated and Unregulated Clinical Trials of Stem Cell Therapies for Stroke

Abstract

Several lines of laboratory investigations reporting solid safety profiles and robust efficacy readouts of stem cells in clinically relevant animal models have advanced stem cell transplantation as an experimental therapy for stroke. Unfortunately, translating laboratory findings into effective clinical trials entails rigorous regulatory examinations, which posed a major challenge in the application of stem cells to patients. As a consequence of this slow pace of clinical entry, and a media-propagated hype narrating stem cells as a “magic bullet”, a dangerous market has been created for unregulated stem cell clinics. These clinics are often guilty of misleading patients and delivering low-quality, even harmful, treatments. Additionally, these medical tourism-purported clinical procedures, which have been performed even in the US, are likely to negatively impact on the true science and clinical value of stem cells. For the full potential of stem cell therapies to be realized, these pressing public misconceptions and regulatory clinical concerns must be addressed. Here, we provide the scientific evidence supporting the safe and effective conduct of stem cells. Arguably, relying on such evidence-based science to dictate the translation of stem cells from the laboratory to the clinic should allow an objective assessment of the risks and the rewards, and the delineation of the hype from hope of this experimental stroke therapy.

Translating intracarotid artery transplantation of bone marrow-derived NCS-01 cells for ischemic stroke: Behavioral and histological readouts and mechanistic insights into stem cell therapy

“…Stem cell research has challenged this paradigm with compelling evidence of exogenous and endogenous repair processes . Transplantation of embryonic, fetal, umbilical, amnion, and induced pluripotent stem cells shows functional improvements in experimental stroke . Adult bone marrow‐derived stem cells, such as endothelial progenitor cells, hematopoietic, and mesenchymal stem cells (MSCs), have expedited the translation of lab‐to‐clinic stem cell therapy due to their logistical ease in isolation and amplification, and being relatively free from ethical concerns .…”

“…7 Transplantation of embryonic, fetal, umbilical, amnion, and induced pluripotent stem cells shows functional improvements in experimental stroke. 8,9 Adult bone marrow-derived stem cells, such as endothelial progenitor cells, hematopoietic, and mesenchymal stem cells (MSCs), have expedited the translation of lab-to-clinic stem cell therapy due to their logistical ease in isolation and amplification, and being relatively free from ethical concerns. 10,11 MSCs have been explored as transplantable donor cells for many experimental models of neurological diseases, 12,13 such as Parkinson's disease, [14][15][16] amyotrophic lateral sclerosis, [17][18][19] Alzheimer's disease, 20,21 and stroke.…”

Regenerative Wound Surgery: Practical Application of Regenerative Medicine in the OR

“…It has been challenging to define clearly the types of processing steps that constitute more than minimal manipulation or uses considered nonhomologous. Historically, as promising new science emerged showing that autologous regenerative cells from bone marrow or adipose tissue could promote healing and regeneration in multiple models of tissue damage, physicians began to experiment with providing ACT for a broad range of acute and chronic conditions outside the purview of FDA‐ and institutional review board–approved clinical trials . However, preparation and use of a patient's own cells for therapy presented a number of significant safety and technical challenges.…”

Potential Therapeutic Mechanisms and Tracking of Transplanted Stem Cells: Implications for Stroke Treatment

“…Furthermore, the cell type, timing, dosage, and route of administration as well as the safety and biocompatibility of the tracker agents must all be considered. Stem cell therapy for the treatment of stroke improves functional recovery and offers the benefit of extending the intervention window via both intracerebral/intracranial (IC) transplantation and peripheral implantation routes, such as intravenous (IV), intra-arterial (IA), and intranasal administration [ 101 ]. IC transplantation is a more invasive procedure that allows precise injection into a chosen location, such as the penumbra and the ischemic core, to guarantee minimal cell delivery to untargeted areas [ 102 , 103 ].…”