Mesenchymal stem cells for the treatment of neurodegenerative and psychiatric disorders

Colpo, Gabriela Delevati; Ascoli, Bruna Maria; Wollenhaupt-Aguiar, Bianca; Pfaffenseller, Bianca; Silva, Emily G.; Cirne-Lima, Elizabeth Obino; Quevedo, Joao L De; Kapczinski, Flávio; Rosa, Adriane Ribeiro

doi:10.1590/0001-3765201520140619

Cited by 27 publications

(14 citation statements)

References 111 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MSCs are potentially able to differentiate into various cell lineages (including neurons), are easy to isolate and expand, have a low tumorigenic risk and low grafting rejection, and lack ethical issues [12–15]. These properties point to MSCs as suitable sources for cell replacement therapy in neurological disorders [16–19]; however, an optimal protocol to induce their conversion into neurons remains unestablished.…”

Section: Introductionmentioning

confidence: 99%

Neuronal Transdifferentiation Potential of Human Mesenchymal Stem Cells from Neonatal and Adult Sources by a Small Molecule Cocktail

Cortés-Medina

Pasantes‐Morales

Aguilera-Castrejon

et al. 2019

Stem Cells International

View full text Add to dashboard Cite

Human mesenchymal stem cells (MSCs) are good candidates for brain cell replacement strategies and have already been used as adjuvant treatments in neurological disorders. MSCs can be obtained from many different sources, and the present study compares the potential of neuronal transdifferentiation in MSCs from adult and neonatal sources (Wharton’s jelly (WhJ), dental pulp (DP), periodontal ligament (PDL), gingival tissue (GT), dermis (SK), placenta (PLAC), and umbilical cord blood (UCB)) with a protocol previously tested in bone marrow- (BM-) MSCs consisting of a cocktail of six small molecules: I-BET151, CHIR99021, forskolin, RepSox, Y-27632, and dbcAMP (ICFRYA). Neuronal morphology and the presence of cells positive for neuronal markers (TUJ1 and MAP2) were considered attributes of neuronal induction. The ICFRYA cocktail did not induce neuronal features in WhJ-MSCs, and these features were only partial in the MSCs from dental tissues, SK-MSCs, and PLAC-MSCs. The best response was found in UCB-MSCs, which was comparable to the response of BM-MSCs. The addition of neurotrophic factors to the ICFRYA cocktail significantly increased the number of cells with complex neuron-like morphology and increased the number of cells positive for mature neuronal markers in BM- and UCB-MSCs. The neuronal cells generated from UCB-MSCs and BM-MSCs showed increased reactivity of the neuronal genes TUJ1, MAP2, NF-H, NCAM, ND1, TAU, ENO2, GABA, and NeuN as well as down- and upregulation of MSC and neuronal genes, respectively. The present study showed marked differences between the MSCs from different sources in response to the transdifferentiation protocol used here. These results may contribute to identifying the best source of MSCs for potential cell replacement therapies.

show abstract

Section: Introductionmentioning

confidence: 99%

Neuronal Transdifferentiation Potential of Human Mesenchymal Stem Cells from Neonatal and Adult Sources by a Small Molecule Cocktail

Cortés-Medina

Pasantes‐Morales

Aguilera-Castrejon

et al. 2019

Stem Cells International

View full text Add to dashboard Cite

show abstract

“…The extracellular matrix molecules may stimulate growth and axonal extension. As modifications of cytokines and neurotrophic factors are also associated with various mental illness, MSC based therapies have also been suggested for psychiatric disorders (Colpo et al, ).…”

Section: Discussionmentioning

confidence: 99%

Functional role of mesenchymal stem cells in the treatment of chronic neurodegenerative diseases

Furno

Mannino

Giuffrida

2017

Journal Cellular Physiology

130

View full text Add to dashboard Cite

Mesenchymal stem cells (MSCs) can differentiate into not only cells of mesodermal lineages, but also into endodermal and ectodermal derived elements, including neurons and glial cells. For this reason, MSCs have been extensively investigated to develop cell-based therapeutic strategies, especially in pathologies whose pharmacological treatments give poor results, if any. As in the case of irreversible neurological disorders characterized by progressive neuronal death, in which behavioral and cognitive functions of patients inexorably decline as the disease progresses. In this review, we focus on the possible functional role exerted by MSCs in the treatment of some disabling neurodegenerative disorders such as Alzheimer's Disease, Amyotrophic Lateral Sclerosis, Huntington's Disease, and Parkinson's Disease. Investigations have been mainly performed in vitro and in animal models by using MSCs generally originated from umbilical cord, bone marrow, or adipose tissue. Positive results obtained have prompted several clinical trials, the number of which is progressively increasing worldwide. To date, many of them have been primarily addressed to verify the safety of the procedures but some improvements have already been reported, fortunately. Although the exact mechanisms of MSC-induced beneficial activities are not entirely defined, they include neurogenesis and angiogenesis stimulation, antiapoptotic, immunomodulatory, and anti-inflammatory actions. Most effects would be exerted through their paracrine expression of neurotrophic factors and cytokines, mainly delivered at damaged regions, given the innate propensity of MSCs to home to injured sites. Hopefully, in the near future more efficacious cell-replacement therapies will be developed to substantially restore disease-disrupted brain circuitry.

show abstract

“…MSCs have been used in pre-clinical models of psychiatry disorders with promising results [156]. For instance, Tfilin et al showed that treatment of an animal model of depression with MSCs increased hippocampal neurogenesis and improved depression-like behavior [157].…”

Section: Immune-based Strategiesmentioning

confidence: 99%

Immune-based strategies for mood disorders: facts and challenges

Colpo

Leboyer

Dantzer

et al. 2017

Expert Review of Neurotherapeutics

Self Cite

View full text Add to dashboard Cite

Inflammation seems to play a role in the pathophysiology of mood disorders, including major depressive disorder (MDD) and bipolar disorder (BD). In the last years several studies have shown increased levels of inflammatory and/or immune markers in patients with mood disorders. Accordingly, the immune system has become a target of interest for the development of biomarkers and therapeutics for mood disorders. Areas covered: Here, we review the evidence showing low-grade inflammation in mood disorders and the studies evaluating immune-based strategies for the treatment of these conditions. Expert commentary: Clinical trials with non-steroidal anti-inflammatory drugs, polyunsaturated acids, N-acetylcysteine, anti-cytokines, physical activity and probiotics have provided promising results in terms of antidepressant efficacy in patients with MDD and BD. Regarding stem cells, only studies with animal models have been performed so far with interesting pre-clinical results. Due to the preliminary nature of the results, most of the clinical studies need to be replicated and/or confirmed in larger clinical settings, embracing the highly heterogeneous pathophysiology of mood disorders.

show abstract

Mesenchymal stem cells for the treatment of neurodegenerative and psychiatric disorders

Cited by 27 publications

References 111 publications

Neuronal Transdifferentiation Potential of Human Mesenchymal Stem Cells from Neonatal and Adult Sources by a Small Molecule Cocktail

Neuronal Transdifferentiation Potential of Human Mesenchymal Stem Cells from Neonatal and Adult Sources by a Small Molecule Cocktail

Functional role of mesenchymal stem cells in the treatment of chronic neurodegenerative diseases

Immune-based strategies for mood disorders: facts and challenges

Contact Info

Product

Resources

About