Autotransplantation of Bone Marrow-Derived Stem Cells as a Therapy for Neurodegenerative Diseases

Abstract

Neurodegenerative diseases are characterized by a progressive degeneration of selective neural populations. This selective hallmark pathology and the lack of effective treatment modalities make these diseases appropriate candidates for cell therapy. Bone marrow-derived mesenchymal stem cells (MSCs) are self-renewing precursors that reside in the bone marrow and may further be exploited for autologous transplantation. Autologous transplantation of MSCs entirely circumvents the problem of immune rejection, does not cause the formation of teratomas, and raises very few ethical or political concerns. More than a few studies showed that transplantation of MSCs resulted in clinical improvement. However, the exact mechanisms responsible for the beneficial outcome have yet to be defined. Possible rationalizations include cell replacement, trophic factors delivery, and immunomodulation. Cell replacement theory is based on the idea that replacement of degenerated neural cells with alternative functioning cells induces long-lasting clinical improvement. It is reasoned that the transplanted cells survive, integrate into the endogenous neural network, and lead to functional improvement. Trophic factor delivery presents a more practical short-term approach. According to this approach, MSC effectiveness may be credited to the production of neurotrophic factors that support neuronal cell survival, induce endogenous cell proliferation, and promote nerve fiber regeneration at sites of injury. The third potential mechanism of action is supported by the recent reports claiming that neuroinflammatory mechanisms play an important role in the pathogenesis of neurodegenerative disorders. Thus, inhibiting chronic inflammatory stress might explain the beneficial effects induced by MSC transplantation. Here, we assemble evidence that supports each theory and review the latest studies that have placed MSC transplantation into the spotlight of biomedical research.

Migration of Neurotrophic Factors-Secreting Mesenchymal Stem Cells Toward a Quinolinic Acid Lesion as Viewed by Magnetic Resonance Imaging

“…MSCs hold a promising future for neurodegenerative disease therapy [29,30]. Whether MSCs can differentiate into nonmesodermal cells and tissues remains controversial [30].…”

Mesenchymal stem cells increase hippocampal neurogenesis and counteract depressive-like behavior

“…[7][8][9] MSCs were therefore suggested as candidates for treating a variety of neurodegenerative diseases, in particular Parkinson's disease, multiple sclerosis, cerebral hemorrhage and brain cancer. [10][11][12][13] Neurogenesis is a continuous process of the formation of new neurons, which occurs in the dentate gyrus in the hippocampus throughout life. Growing evidence has recently linked impaired neurogenesis in the hippocampus with affective disorders, including depression.…”

Stem cell therapy in intracerebral hemorrhage rat model

“…As stated in previous sections, different stem cell types have different attributes, and knowledge is in its youth about how all these divergences may affect ICH outcome. Bao et al [113] Col Ⅶ hBMSC (Flk-1+) 24 h 2 × 10 5 15 BP Chen et al [120] Col Ⅳ ASC 48 h 3 × 10 6 10 LV Fatar et al [112] Col Ⅳ hASC 24 h 3 × 10 6 500 TV Jeon et al [110] Col Ⅶ ASC extract 1 h --IP Jeong et al [138] Col Ⅳ hNSC 24 h 5 × 10 6 500 TV Kim et al [125] Col Ⅶ hASC 24 h 3 × 10 6 2000 TV Lee et al [126] Col Ⅶ hNSC 2 h; 24 h 5 × 10 6 (TV); 1 × 10 6 (IC) 500 (TV); 2 (BP) TV; BP Li et al [139] Col Ⅶ NSC 2 h; 7 h; 14 h; 21 h; 27 h 4 × 10 6 400 CA Liang et al [114] Col Ⅳ BMSC 24 h 1 × 10 6 10 BP Liao et al [66] Col Ⅶ hUCSC 24 h 2 × 10 5 10 BP Nan et al [158] Col Ⅶ hUCB 24 h 2.4 × 10 6 -3.2 × 10 6 500 SV Otero et al [134] Col Ⅳ BMSC 72 h 2 × 10 6 10 BP Otero et al [115] Col Ⅳ BMSC 2 m 5 × 10 6 15 BP Otero et al [111] Col Ⅳ BMSC 2 h 2 × 10 6 15 BP Qin et al [116] Col Ⅶ iPSC 24 h 2 × 10 6 10 BP Qin et al [135] Col Ⅶ iPSC 24 h 1 × 10 6 10 BP Seghatoleslam et al [124] Col [140] ABI BMSC 24 h 1 × 10 6 100 CA Seyfried et al [122] ABI BMSC 24 h 5 × 10…”

“…Despite the numerous promising preclinical assays including neuroprotective, antihypertensive, and anti-inflammatory drugs, only symptomatic treatments are currently available [2,3] , which motivates the search for new alternatives. In this context, cell therapy emerged as a promising tool [4][5][6] . However, more than a decade has passed, and there is still much to be learned not only about stem cells, but also about ICH itself, and how these two pieces come together.…”