Bringing Neural Cell Therapies to the Clinic: Past and Future Strategies

Abstract

Cell replacement therapy in the nervous system has a rich history, with ∼40 years of research and ∼30 years of clinical experience. There is compelling evidence that appropriate cells can integrate and function in the dysfunctioning human nervous system, but the clinical results are mixed in practice. A number of factors conspire to vary patient outcome: the indication, cell source, patient selection, and team performing transplantation are all variables that can affect efficacy. Most early clinical trials have used fetal cells, a limited cell source that resists scale and standardization. Direct fetal cell transplantation creates significant challenges to commercialization that is the ultimate goal of an effective cell therapy. One approach to help scale and standardize fetal cell preparations is the expansion of neural cells in vitro. Expansion is achieved by transformation or through the application of mitogens before cryopreservation. Recently, neural cells derived from pluripotent stem cells have provided a scalable alternative. Pluripotent stem cells are desirable for manufacturing but present alternative concerns and manufacturing obstacles. All cell sources require robust and reproducible manufacturing to make nervous system cell replacement therapy an option for patients. Here, we discuss the challenges and opportunities for cell replacement in the nervous system. In this review, we give an overview of completed and ongoing neural cell transplantation clinical trials, and we discuss the challenges and opportunities for future cell replacement trials with a particular focus on pluripotent stem cell-derived therapies.

Stem Cells and Regenerative Medicine

“…Another difference from organ transplantation is that healthy cells may be taken from the same person, without a problem of tissue compatibility. [16] On the other hand, cord blood cells can be used for the same purposes. [16] However, cord blood cells also have limited use.…”

“…[16] On the other hand, cord blood cells can be used for the same purposes. [16] However, cord blood cells also have limited use. [16] If the experiments succeed, stem cell therapies will not require extensive surgery or drug administration.…”

Engineering molecular imaging strategies for regenerative medicine

“…for cell-based cancer immunotherapy, 62 cardiac cell therapy, 63 islet cell therapy for type II diabetes mellitus, 61 retinal progenitor cell therapy for macular degeneration, 56 hepatocyte cell therapy, 64 cell therapy for the nervous system, 65 and mesenchymal stem cell (MSC) therapy for a wide range of diseases. 66 Consistent with this, forecasts suggest that the number of studies using adult and PSC will continue to grow because of the increasing need for treatments for chronic diseases.…”

Neurons from human mesenchymal stem cells display both spontaneous and stimuli responsive activity

“…Only few studies have shown that hMSC-derived neurons are functionally active upon chemical or electrical excitation [21]. Because of the complexity of the nervous system, prior to use hMSC derived neurons as a tool for disease modeling or regenerative applications, the activity pattern and functional synapse formations of these neurons have to be defined to move the neuronal differentiation study a step further [22][23][24].…”