Stroke – Therapy and Treatment

Discov Med. 2013 Aug;16(86):37-43.

Adipose tissue-derived stem cells in stroke treatment: from bench to bedside.

Gutiérrez-Fernández M¹, Rodríguez-Frutos B, Otero-Ortega L, Ramos-Cejudo J, Fuentes B, Díez-Tejedor E.

Abstract

More recently, growing interests have brought cell therapy to the forefront of promising new approaches towards efficacious treatment for stroke. Of all cell-types, adipose tissue-derived mesenchymal stem cells (AD-MSC) are considered good candidates for stroke treatment because of their abundance and easy harvesting without invasive surgery from healthy donors. A wide number of experimental studies have demonstrated the potential of AD-MSC administration for improving functional deficits and have led to the first clinical trials in stroke patients. Trophic factor release and paracrine interactions, transdifferentiation potential, and immunomodulatory effects have all been cited as the main functional mechanisms involved in AD-MSC therapy. These properties make AD-MSC therapy of special interest in fomenting the enhancement of natural brain repair mechanisms such as neurogenesis, gliagenesis, oligodendrogenesis, axonal sprouting, nerve repair, and angiogenesis. This review will focus on studies showing promising results of AD-MSC in stroke treatment.

Cell Transplant. 2014;23(4-5):541-7. doi: 10.3727/096368914X678409.

The use of ADSCs as a treatment for chronic stroke.

Chan TM¹, Harn HJ, Lin HP, Chiu SC, Lin PC, Wang HI, Ho LI, Chuu CP, Chiou TW, Hsieh AC, Chen YW, Ho WY, Lin SZ.

Abstract

Stroke is one of the disorders for which clinically effective therapeutic modalities are most needed, and numerous ways have been explored to attempt to investigate their feasibilities. However, ischemic- or hemorrhagic-induced inflammatory neuron death causes irreversible injuries and infarction regions, and there are currently no truly effective drugs available as therapy. It is therefore urgent to be able to provide a fundamental treatment method to regenerate neuronal brain cells, and therefore, the use of stem cells for curing chronic stroke could be a major breakthrough development. In this review, we describe the features and classification of stroke and focus on the benefits of adipose tissue-derived stem cellsand their applications in stroke animal models. The results show that cell-based therapies have resulted in significant improvements in neuronal behaviors and functions through different molecular mechanisms, and no safety problems have so far arisen after transplantation. Further, we propose a clinical possibility to create a homing niche by reducing the degree of invasive intracerebroventricular transplantation and combining it with continuous intravenous administration to achieve a complete cure.

Cytotherapy. 2011 Jul;13(6):675-85. doi: 10.3109/14653249.2010.549122. Epub 2011 Jan 13.

Comparison of mesenchymal stem cells from adipose tissue and bone marrow for ischemic stroke therapy.

Ikegame Y¹, Yamashita K, Hayashi S, Mizuno H, Tawada M, You F, Yamada K, Tanaka Y, Egashira Y, Nakashima S, Yoshimura S, Iwama T.

Abstract

BACKGROUND AIMS:

Transplantation of mesenchymal stromal cells (MSC) derived from bone marrow (BM) or adipose tissue is expected to become a cell therapy for stroke. The present study compared the therapeutic potential of adipose-derived stem cells (ASC) with that of BM-derived stem cells (BMSC) in a murine stroke model.

METHODS:

ASC and BMSC were isolated from age-matched C57BL/6J mice. These MSC were analyzed for growth kinetics and their capacity to secrete trophic factors and differentiate toward neural and vascular cell lineages in vitro. For in vivo study, ASC or BMSC were administrated intravenously into recipient mice (1 × 10(5) cells/mouse) soon after reperfusion following a 90-min middle cerebral artery occlusion. Neurologic deficits, the degree of infarction, expression of factors in the brain, and the fate of the injected cells were observed.

RESULTS:

ASC showed higher proliferative activity with greater production of vascular endothelial cell growth factor (VEGF) and hepatocyte growth factor (HGF) than BMSC. Furthermore, in vitro conditions allowed ASC to differentiate into neural, glial and vascular endothelial cells. ASC administration showed remarkable attenuation of ischemic damage, although the ASC were not yet fully incorporated into the infarct area. Nonetheless, the expression of HGF and angiopoietin-1 in ischemic brain tissue was significantly increased in ASC-treated mice compared with the BMSC group.

CONCLUSIONS:

Compared with BMSC, ASC have great advantages for cell preparation because of easier and safer access to adipose tissue. Taken together, our findings suggest that ASC would be a more preferable source for cell therapy for brain ischemia than BMSC.

Neuropsychiatr Dis Treat. 2016 Jun 2;12:1287-93. doi: 10.2147/NDT.S104917. eCollection 2016.

Intravenous administration of adipose tissue-derived stem cells enhances nerve healing and promotes BDNF expression via the TrkB signaling in a rat stroke model.

Li X¹, Zheng W², Bai H¹, Wang J³, Wei R¹, Wen H³, Ning H³.

Abstract

Previous studies have shown the beneficial effects of adipose-derived stem cells (ADSCs) transplantation in stroke. However, the molecular mechanism by which transplanted ADSCs promote nerve healing is not yet elucidated. In order to make clear the molecular mechanism for the neuroprotective effects of ADSCs and investigate roles of the BDNF-TrkB signaling in neuroprotection of ADSCs, we, therefore, examined the neurological function, brain water content, and the protein expression in middle cerebral artery occlusion (MCAO) rats with or without ADSCs transplantation. ADSCs were transplanted intravenously into rats at 30 minutes after MCAO. K252a, an inhibitor of TrkB, was administered into rats by intraventricular and brain stereotaxic injection. Modified neurological severity score tests were performed to measure behavioral outcomes. The results showed that ADSCs significantly alleviated neurological deficits and reduced brain water content in MCAO rats. The protein expression levels of BDNF and TrkB significantly increased in the cortex of MCAO rats with ADSCs treatment. However, K252a administration reversed the ADSCs-induced elevation of BDNF, TrkB, and Bcl-2 and reduction of Bax protein in MCAO rats. ADSCs promote BDNF expression via the TrkB signaling and improve functional neurological recovery in stroke rats.

KEYWORDS:

TrkB; adipose tissue-derived stem cells; brain-derived neurotrophic factor; stroke

Arterioscler Thromb Vasc Biol. 2009 Nov;29(11):1723-9. doi: 10.1161/ATVBAHA.109.187179. Epub 2009 Jul 23.

Adipose tissue-derived stem cells: characterization and potential for cardiovascular repair.

Madonna R¹, Geng YJ, De Caterina R.

Abstract

Experimental studies have shown that cardiac transfer of unfractionated or partially purified bone marrow cells, as well as stem cells and progenitor cells derived from the bone marrow or peripheral blood, can enhance functional recovery after an acute myocardial infarction. However, the relatively low abundance, small tissue volume, difficult accessibility, and disease-related malfunction of bone marrow-derived stem cellshamper their clinical usefulness. Numerous studies have provided evidence that stromal cells derived from the adipose tissue (adipose tissue-derived stromal cells [ADSCs]) contain a population of adult multipotent mesenchymal stem cells and endothelial progenitor cells that can differentiate into several lineages, including endothelial cells, smooth muscle cells, and cardiomyocytes. The similarities between stem cellsextracted from the bone marrow and the adipose tissue suggest the potential for the adipose tissue to act as an alternative, and perhaps preferable, cell source for repairing damaged tissues, such as the ischemic or infarcted heart. We have here reviewed the medical literature describing molecular and functional characterization, differentiation, potential role, and results obtained so far using ADSCs in tissue repair, with a particular focus on the role for ADSCs in cardiovascular repair and regeneration.