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

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Lorena V. Cortés-Medina ◽  
Herminia Pasantes-Morales ◽  
Alejandro Aguilera-Castrejon ◽  
Arturo Picones ◽  
Cesar O. Lara-Figueroa ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cells ◽  
Neuronal Morphology ◽  
Cell Replacement ◽  
Neuronal Markers ◽  
Dental Tissues ◽  
Neuronal Genes ◽  
Different Sources ◽  
Number Of Cells

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.

Myogenic Properties of Human Mesenchymal Stem Cells Derived from Three Different Sources

2012 ◽  
Vol 21 (1) ◽  
pp. 153-173 ◽  
Author(s):  
Anabel S. De La Garza-Rodea ◽  
Ietje Van Der Velde-Van Dijke ◽  
Hester Boersma ◽  
Manuel A. F. V. Gonçalves ◽  
Dirk W. Van Bekkum ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cells ◽  
Different Sources

scholarly journals Expression of Neural Markers by Undifferentiated Mesenchymal-Like Stem Cells from Different Sources

2014 ◽  
Vol 2014 ◽  
pp. 1-16 ◽  
Author(s):  
Dana Foudah ◽  
Marianna Monfrini ◽  
Elisabetta Donzelli ◽  
Stefania Niada ◽  
Anna T. Brini ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Periodontal Ligament Stem Cells ◽  
Neural Repair ◽  
Neuronal Markers ◽  
Cell Based Therapy ◽  
Human Dental Pulp ◽  
Neural Markers ◽  
Spontaneous Expression ◽  
Different Sources

The spontaneous expression of neural markers, already demonstrated in bone marrow (BM) mesenchymal stem cells (MSCs), has been considered as evidence of the MSCs’ predisposition to differentiate toward neural lineages, supporting their use in stem cell-based therapy for neural repair. In this study we have evaluated, by immunocytochemistry, immunoblotting, and flow cytometry experiments, the expression of neural markers in undifferentiated MSCs from different sources: human adipose stem cells (hASCs), human skin-derived mesenchymal stem cells (hS-MSCs), human periodontal ligament stem cells (hPDLSCs,) and human dental pulp stem cells (hDPSCs). Our results demonstrate that the neuronal markersβIII-tubulin and NeuN, unlike other evaluated markers, are spontaneously expressed by a very high percentage of undifferentiated hASCs, hS-MSCs, hPDLSCs, and hDPSCs. Conversely, the neural progenitor marker nestin is expressed only by a high percentage of undifferentiated hPDLSCs and hDPSCs. Our results suggest that the expression ofβIII-tubulin and NeuN could be a common feature of stem cells and not exclusive to neuronal cells. This could result in a reassessment of the use ofβIII-tubulin and NeuN as the only evidence proving neuronal differentiation. Further studies will be necessary to elucidate the relevance of the spontaneous expression of these markers in stem cells.

scholarly journals Radiation Responses of Human Mesenchymal Stem Cells Derived From Different Sources

Dose-Response ◽  
2019 ◽  
Vol 17 (4) ◽  
pp. 155932581989321 ◽  
Author(s):  
Ningning He ◽  
Changyan Xiao ◽  
Yuxiao Sun ◽  
Yan Wang ◽  
Liqing Du ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Radiation Resistance ◽  
Human Mesenchymal Stem Cells ◽  
Human Mscs ◽  
Potential Biomarker ◽  
Radiation Induced ◽  
Stem Cell Treatment ◽  
Comparison Of The Results ◽  
Different Sources

Mesenchymal stem cells (MSCs) derived from different tissues may aid in the regeneration of radiation-induced organ lesions; however, the radiation responses of human MSCs from different sources are unknown. In our study, a comparison of the results from cell proliferation, apoptosis, cell cycle, DNA damage, and DNA repair assays consistently showed that MSCs derived from adipose tissue possess a significantly stronger radiation resistance capacity than MSCs derived from umbilical cord and gingival, which is accompanied by a higher level of phosphorylated signal transducer and activator of transcription 3 (Stat3) expression. This reminds us Stat3 could be a potential biomarker of radiation resistance. These findings provide a better understanding of radiation-induced biologic responses in MSCs and may lead to the development of better strategies for stem cell treatment and cancer therapy.

scholarly journals Dental Tissue-Derived Human Mesenchymal Stem Cells and Their Potential in Therapeutic Application

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Lu Gan ◽  
Ying Liu ◽  
Dixin Cui ◽  
Yue Pan ◽  
Liwei Zheng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cells ◽  
Preclinical Studies ◽  
Dental Tissue ◽  
Differentiation Potential ◽  
Dental Tissues ◽  
Lineage Differentiation ◽  
Cell Based Therapy

Human mesenchymal stem cells (hMSCs) are multipotent cells, which exhibit plastic adherence, express specific cell surface marker spectrum, and have multi-lineage differentiation potential. These cells can be obtained from multiple tissues. Dental tissue-derived hMSCs (dental MSCs) possess the ability to give rise to mesodermal lineage (osteocytes, adipocytes, and chondrocytes), ectodermal lineage (neurocytes), and endodermal lineages (hepatocytes). Dental MSCs were first isolated from dental pulp of the extracted third molar and till now they have been purified from various dental tissues, including pulp tissue of permanent teeth and exfoliated deciduous teeth, apical papilla, periodontal ligament, gingiva, dental follicle, tooth germ, and alveolar bone. Dental MSCs are not only easily accessible but are also expandable in vitro with relative genomic stability for a long period of time. Moreover, dental MSCs have exhibited immunomodulatory properties by secreting cytokines. Easy accessibility, multi-lineage differentiation potential, and immunomodulatory effects make dental MSCs distinct from the other hMSCs and an effective tool in stem cell-based therapy. Several preclinical studies and clinical trials have been performed using dental MSCs in the treatment of multiple ailments, ranging from dental diseases to nondental diseases. The present review has summarized dental MSC sources, multi-lineage differentiation capacities, immunomodulatory features, its potential in the treatment of diseases, and its application in both preclinical studies and clinical trials. The regenerative therapeutic strategies in dental medicine have also been discussed.

scholarly journals Hypoxic-Mediated Oxidative Stress Condition and Hydroxyapatite-Inducing Osteogenic Differentiation of Human Mesenchymal Stem Cells: A Mathematical Modeling Study

2020 ◽  
Vol 16 (6) ◽  
pp. 910-921
Author(s):  
Yan Chao Cui ◽  
Yu Sheng Qiu ◽  
Qiong Wu ◽  
Gang Bu ◽  
Seoh Wei Teh ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cells ◽  
Bone Cell ◽  
Culture Conditions ◽  
Cell Replacement ◽  
Hypoxic Conditions ◽  
Replacement Treatment ◽  
Osteogenic Induction ◽  
Vessel Network

Avascular necrosis (AVN) of the bones remains a major clinical challenge. Fractures in the talus, the scaphoid, and the neck of the femur are especially challenging to heal due to the low blood vessel network and the lack of collateral blood supply. These fractures are associated with high rates of nonunion and increased infections that require repeated operations. Conventional treatments by autografting or allografting bone replacement and synthetic bone implants have limitations, including the invasiveness of operative procedures, tissue supply insufficiency, and the risk of host rejection. The advancement in tissue engineering has revealed the potential of stem cells as restorative agents for bone injuries. The administration of mesenchymal stem cells (MSCs) into the talus, the scaphoid, and the neck of the femur could produce enhanced osteogenesis via the manipulation of MSC culture conditions. In this study, we used hydroxyapatite as the nanomaterial, and hypoxic milieu to enhance MSC differentiation capacity into the osteogenic lineage, allowing for more rapid and efficient bone cell replacement treatment. Our results demonstrate 1% oxygen and 12.5 μg/mL of hydroxyapatite (HAP) as the optimal conditions to incorporate the osteogenic medium for the osteogenic induction of MSCs. We also established a proof of concept that the addition of HAP and hypoxic conditions could augment the osteoinductive capacity of MSCs. We also developed an accurate mathematical model to support future bone cell replacement therapy.

scholarly journals Vitamin D Effects on Osteoblastic Differentiation of Mesenchymal Stem Cells from Dental Tissues

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Francesca Posa ◽  
Adriana Di Benedetto ◽  
Graziana Colaianni ◽  
Elisabetta A. Cavalcanti-Adam ◽  
Giacomina Brunetti ◽  
...  
Keyword(s):  
Stem Cells ◽  
Vitamin D ◽  
Mesenchymal Stem Cells ◽  
Adult Stem Cells ◽  
Human Mesenchymal Stem Cells ◽  
Osteoblastic Differentiation ◽  
Skeletal System ◽  
Dihydroxyvitamin D ◽  
Dental Tissues ◽  
Immature Form

1α,25-Dihydroxyvitamin D3(1,25(OH)2D3), the active metabolite of vitamin D (Vit D), increases intestinal absorption of calcium and phosphate, maintaining a correct balance of bone remodeling. Vit D has an anabolic effect on the skeletal system and is key in promoting osteoblastic differentiation of human Mesenchymal Stem Cells (hMSCs) from bone marrow. MSCs can be also isolated from the immature form of the tooth, the dental bud: Dental Bud Stem Cells (DBSCs) are adult stem cells that can effectively undergo osteoblastic differentiation. In this work we investigated the effect of Vit D on DBSCs differentiation into osteoblasts. Our data demonstrate that DBSCs, cultured in an opportune osteogenic medium, differentiate into osteoblast-like cells; Vit D treatment stimulates their osteoblastic features, increasing the expression of typical markers of osteoblastogenesis like RUNX2 and Collagen I (Coll I) and, in a more important way, determining a higher production of mineralized matrix nodules.

scholarly journals The Different Molecular Code in Generation of Dopaminergic Neurons from Astrocytes and Mesenchymal Stem Cells

2021 ◽  
Vol 22 (22) ◽  
pp. 12141
Author(s):  
Nana Wang ◽  
Xingrui Ji ◽  
Yue Wu ◽  
Shaocong Zhou ◽  
Huiyu Peng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Transcription Factor ◽  
Adipose Tissue ◽  
Dopaminergic Neurons ◽  
Cell Replacement Therapy ◽  
Cell Replacement ◽  
Neuronal Markers ◽  
Molecular Code

Transplantation of exogenous dopaminergic (DA) neurons is an alternative strategy to replenish DA neurons that have lost along the course of Parkinson’s disease (PD). From the perspective of ethical acceptation, the source limitations, and the intrinsic features of PD pathology, astrocytes (AS) and mesenchymal stem cells (MSCs) are the two promising candidates of DA induction. In the present study, we induced AS or MSCs primary culture by the combination of the classical transcription-factor cocktails Mash1, Lmx1a, and Nurr1 (MLN), the chemical cocktails (S/C/D), and the morphogens SHH, FGF8, and FGF2 (S/F8/F2); the efficiency of induction into DA neurons was further analyzed by using immunostaining against the DA neuronal markers. AS could be efficiently converted into the DA neurons in vitro by the transcriptional regulation of MLN, and the combination with S/C/D or S/F8/F2 further increased the conversion efficiency. In contrast, MSCs from umbilical cord (UC-MSCs) or adipose tissue (AD-MSCs) showed moderate TH immunoreactivity after the induction with S/F8/F2 instead of with MLN or S/C/D. Our data demonstrated that AS and MSCs held lineage-specific molecular codes on the induction into DA neurons and highlighted the unique superiority of AS in the potential of cell replacement therapy for PD.

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