Bone-marrow-derived mesenchymal stem cell therapy for neurodegenerative diseases.
BACKGROUND
Stem-cell-based therapy is a promising new approach to handling neurodegenerative diseases. One of the most promising cellular sources is bone-marrow-derived mesenchymal stem cells (MSCs) also termed multipotent stromal cells. MSCs represent an autologous source and are abundant and non-tumorigenic. Additionally, MSCs possess the useful characteristics of homing and chemokine secretion.


OBJECTIVE
Since neurodegenerative diseases have many pathological processes in common, a specific therapeutic agent could potentially ameliorate the symptoms of several distinct neurodegenerative diseases. In this review we demonstrate the wide variety of mechanisms by which MSCs can influence neurodegenerative processes.


CONCLUSIONS
The mechanisms by which transplanted MSCs influence neurodegenerative diseases can be broadly classified as cellular replacement or paracrine secretion, with the latter subdivided into trophic factor secretion or immunomodulation by cytokines. Emerging research suggests that genetic manipulations before transplantation could enhance the therapeutic potential of MSCs. Such manipulation could turn the cells into a 'Trojan horse', to deliver specific proteins, or promote reprogramming of the MSCs into the neural lineage. Clinical trials testing MSC-based therapies for familial amyotrophic lateral sclerosis and multiple sclerosis are in progress.
Sadan
Ofer
O
Neurosciences Laboratory, Felsenstein Medical Research Center, Rabin Medical Center, Petah Tikva, Israel.
Melamed
Eldad
E
Offen
Daniel
D
D000818:Animals; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D002465:Cell Movement; D003131:Combined Modality Therapy; D016207:Cytokines / Q000276:immunology; D015316:Genetic Therapy; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000276:immunology / Q000601:surgery*; D055495:Neurogenesis; D009474:Neurons / Q000276:immunology / Q000637:transplantation*; D019899:Paracrine Communication; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D016207:Cytokines