Regenerative Stem Cell Therapy for Neurodegenerative Diseases: An Overview

Abstract

Neurodegenerative diseases resulting from the progressive loss of structure and/or function of neurons contribute to different paralysis degrees and loss of cognition and sensation. The lack of successful curative therapies for neurodegenerative disorders leads to a considerable burden on society and a high economic impact. Over the past 20 years, regenerative cell therapy, also known as stem cell therapy, has provided an excellent opportunity to investigate potentially powerful innovative strategies for treating neurodegenerative diseases. This is due to stem cells’ capability to repair injured neuronal tissue by replacing the damaged or lost cells with differentiated cells, providing a conducive environment that is in favor of regeneration, or protecting the existing healthy neurons and glial cells from further damage. Thus, in this review, the various types of stem cells, the current knowledge of stem-cell-based therapies in neurodegenerative diseases, and the recent advances in this field are summarized. Indeed, a better understanding and further studies of stem cell technologies cause progress into realistic and efficacious treatments of neurodegenerative disorders.

Mesenchymal Stem Cell-Derived Exosomes Ameliorate Alzheimer’s Disease Pathology and Improve Cognitive Deficits

“…In rodent AD models, MSC transplantation has been reported to reduce Aβ deposition, stimulate neurogenesis, improve spatial learning and memory deficits [ 16 ]. AD, as a neurodegenerative disorder, is characterized by mass neuronal and synaptic loss; therefore, regeneration of neuronal circuits by exogenous MSCs is a rational therapeutic strategy [ 17 ]. Nevertheless, the risks of tumor formation, immune rejection, and infusional toxicity in MSC transplantation remain unresolved.…”

Stem Cells: Innovative Therapeutic Options for Neurodegenerative Diseases?

“…In addition to these preeminent scientific issues, another substantial matter that needs to be evaluated is represented by the high running costs of stem cell therapy. Indeed, the production phases must comply with specific GMP standards [98], which involve appropriate materials, equipment, personnel, and facilities. Specifically, a study conducted in 2020, which estimated manufacturing and development costs for cell-based therapies, pointed out that the expenses for PSCs production are around 500,000 s [112].…”

“…Numerous clinical trials evaluated safety and feasibility of intraspinal, intrathecal and intracerebral MSCs transplantation; for instance, Mazzini et al [97] experimented implantation of these cells into the dorsal spinal cord, showing no immediate or long-complications in a follow-up period of 9 years. Furthermore, other clinical trials are focused on the exogenous transplantation of NSCs due to valid data indicating the slowing down progression of ALS cells injection into subjects' spinal cord [98]. Subsequently, we report the current clinical trials on stem cell therapy for ALS (Table 2).…”

“…A useful candidate stem-cell equivalent source might be represented by MSCs that have been shown to reduce dopamine depletion and rebuild the damaged striatal dopaminergic nerve terminal network in a PD animal model [98]. A previous pilot clinical trial performed MSC transplantations in the lateral ventricles' walls of PD patients and reported promising functional recovery with no adverse effects and improved dyskinesias [107].…”

Naive BM-derived stem cells (Neuro-Cells) may modify acute and chronic neurodegenerative disorders by modulating macrophage behaviors

“…Stem cells can be harvested out of adipose tissue, bone marrow, olfactory mucosa, umbilical cord blood, and embryonic tissue, as well as out of special niches in organs, all varying in their regenerative capacity and potency. Their specific differences in biological properties might be an important consideration for their selection in regenerative medicine [52] . Applying autologous stem cells is preferred over allogeneic preparations, as these come with a risk of immunological incompatibility.…”