scholarly journals Use of adult mesenchymal stromal cells in tissue repair: impact of physical exercise

2019 ◽  
Vol 317 (4) ◽  
pp. C642-C654 ◽  
Author(s):  
Celine Bourzac ◽  
Morad Bensidhoum ◽  
Stephane Pallu ◽  
Hugues Portier
Keyword(s):  
Physical Exercise ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Tissue Repair ◽  
Mechanical Stimulus ◽  
Great Promise ◽  
Muscular Tissue ◽  
Beneficial Effects ◽  
Tissue Recovery

Physical exercise (PE) has unquestionable beneficial effects on health, which likely extend into several organ-to-cell physiological processes. At the cell scale, endogenous mesenchymal stromal cells (MSCs) contribute to tissue repair, although their repair capacities may be insufficient in paucicellular or severely damaged tissues. For this reason, MSC transplantation holds great promise for tissue repair. With the goals of understanding if PE has beneficial effects on MSC biology and if PE potentiates their role in tissue repair, we reviewed literature reports regarding the effects of PE on MSC properties (specifically, proliferation, differentiation, and homing) and of a combination of PE and MSC transplantation on tissue repair (specifically neural, cartilage, and muscular tissues). Contradictory results have been reported; interpretation is complicated because various and different species, cell sources, and experimental protocols, specifically exercise programs, have been used. On the basis of these data, the effects of exercise on MSC proliferation and differentiation depend on exercise characteristics (type, intensity, duration, etc.) and on the characteristics of the tissue from which the MSCs were collected. For the in vitro studies, the level of strain (and other details of the mechanical stimulus), the time elapsed between the end of exposure to strain and MSC collection, the age of the donors, as well as the passage number at which the MSCs are evaluated also play a role. The combination of PE and MSC engraftment improves neural, cartilage, and muscular tissue recovery, but it is not clear whether the effects of MSCs and exercise are additive or synergistic.

scholarly journals Enhancing the Migration Ability of Mesenchymal Stromal Cells by Targeting the SDF-1/CXCR4 Axis

2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
Leah A. Marquez-Curtis ◽  
Anna Janowska-Wieczorek
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Tissue Repair ◽  
Inflammatory Responses ◽  
Surface Expression ◽  
Trophic Factors ◽  
Migration Ability ◽  
Therapeutic Benefits

Mesenchymal stromal cells (MSCs) are currently being investigated in numerous clinical trials of tissue repair and various immunological disorders based on their ability to secrete trophic factors and to modulate inflammatory responses. MSCs have been shown to migrate to sites of injury and inflammation in response to soluble mediators including the chemokine stromal cell-derived factor-(SDF-)1, but during in vitro culture expansion MSCs lose surface expression of key homing receptors particularly of the SDF-1 receptor, CXCR4. Here we review studies on enhancement of SDF-1-directed migration of MSCs with the premise that their improved recruitment could translate to therapeutic benefits. We describe our studies on approaches to increase the CXCR4 expression in in vitro-expanded cord blood-derived MSCs, namely, transfection, using the commercial liposomal reagent IBAfect, chemical treatment with the histone deacetylase inhibitor valproic acid, and exposure to recombinant complement component C1q. These methodologies will be presented in the context of other cell targeting and delivery strategies that exploit pathways involved in MSC migration. Taken together, these findings indicate that MSCs can be manipulated in vitro to enhance their in vivo recruitment and efficacy for tissue repair.

scholarly journals Isolation, expansion and differentiation of mesenchymal stromal cells from rabbits' bone marrow

2016 ◽  
Vol 36 (5) ◽  
pp. 423-430 ◽  
Author(s):  
Renato B. Eleotério ◽  
Rodrigo V. Sepúlveda ◽  
Emily C.C. Reis ◽  
Fabrício L. Valente ◽  
Andréa P.B. Borges
Keyword(s):  
Bone Marrow ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Tissue Repair ◽  
Mononuclear Cells ◽  
Culture Media ◽  
Rabbit Model ◽  
Proliferation Rate ◽  
Media Formulation

Abstract: Tissue engineering has been a fundamental technique in the regenerative medicine field, once it permits to build tri-dimensional tissue constructs associating undifferentiated mesenchymal cells (or mesenchymal stromal cells - MSCs) and scaffolds in vitro. Therefore, many studies have been carried out using these cells from different animal species, and rabbits are often used as animal model for in vivo tissue repair studies. However, most of the information available about MSCs harvesting and characterization is about human and murine cells, which brings some doubts to researchers who desire to work with a rabbit model in tissue repair studies based on MSCs. In this context, this study aimed to add and improve the information available in the scientific literature providing a complete technique for isolation, expansion and differentiation of MSCs from rabbits. Bone marrow mononuclear cells (BMMCs) from humerus and femur of rabbits were obtained and to evaluate their proliferation rate, three different culture media were tested, here referred as DMEM-P, DMEM´S and α-MEM. The BMMCs were also cultured in osteogenic, chondrogenic and adipogenic induction media to prove their multipotentiality. It was concluded that the techniques suggested in this study can provide a guideline to harvest and isolate MSCs from bone marrow of rabbits in enough amount to allow their expansion and, based on the laboratory experience where the study was developed, it is also suggested a culture media formulation to provide a better cell proliferation rate with multipotentiality preservation.

Melatonin pretreatment of human adipose tissue-derived mesenchymal stromal cells enhances their prosurvival and protective effects on human kidney cells

2015 ◽  
Vol 308 (12) ◽  
pp. F1474-F1483 ◽  
Author(s):  
Jing Zhao ◽  
Yoon Kow Young ◽  
Julie Fradette ◽  
Nicoletta Eliopoulos
Keyword(s):  
Adipose Tissue ◽  
Cell Therapy ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Tissue Injury ◽  
Human Kidney ◽  
Great Promise ◽  
Kidney Cells ◽  
Protective Effects

The efficacy of cell therapy for many diseases can be limited by the poor survival of implanted cells in an environment of tissue injury. Melatonin has been reported to have antioxidative and antiapoptotic effects. Adipose tissue-derived mesenchymal stromal cells (ASCs), cells easily obtained in high amounts and with minimal discomfort, have shown great promise in cell therapy applications, such as in acute kidney injury. We hypothesized that melatonin pretreatment of human ASCs (hASCs) would improve their renoprotective and prosurvival effects. We therefore investigated the action of melatonin on hASCs, as well as the effect of the resulting hASCs-conditioned media (CM) on human kidney cells exposed to oxidative and apoptotic injury-provoking doses of cisplatin. Our results demonstrated that pretreatment of hASCs with melatonin, 100 μM for 3 h, significantly increased their proliferation and their expression of prosurvival P-Erk1/2 and P-Akt, and of antioxidative enzymes catalase and heme oxygenase (HO)-1. In addition, the CM from hASCs pretreated with melatonin provoked a significantly higher proliferation and migration of HK-2 human kidney epithelial cells. Furthermore, this CM exerted significantly higher prosurvival and antiapoptotic actions on HK-2 cells exposed to cisplatin in vitro. Western blot analysis showed higher expression of P-Erk1/2, Bcl-2, SOD-1, and HO-1 in the HK-2 cells exposed to cisplatin in the presence of CM from melatonin-pretreated hASCs. In sum, our study revealed that in vitro pretreatment of hASCs with melatonin may significantly enhance their survival and their therapeutic effectiveness on injured tissue.

scholarly journals Effect of Highly Loaded Nanohydroxyapatite Composite Scaffolds Prepared via Melt Extrusion Additive Manufacturing on the Osteogenic Differentiation of Human Mesenchymal Stromal Cells

2021 ◽  
Author(s):  
María Cámara-Torres ◽  
Ravi Sinha ◽  
Alberto Sanchez ◽  
Pamela Habibovic ◽  
Alessandro Patelli ◽  
...  
Keyword(s):  
Additive Manufacturing ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Matrix Composition ◽  
Osteogenic Potential ◽  
Great Promise ◽  
Melt Extrusion ◽  
Human Mesenchymal Stromal Cells ◽  
Highly Loaded

AbstractThe field of bone tissue engineering seeks to mimic the bone extracellular matrix composition, balancing the organic and inorganic components. In this regard, additive manufacturing (AM) of highly loaded polymer-calcium phosphate (CaP) composites holds great promise towards the design of bioactive scaffolds. Yet, the biological performance of such scaffolds is still poorly characterized. In this study, melt extrusion AM (ME-AM) was used to fabricate poly(ethylene oxide terephthalate)/poly(butylene terephthalate) (PEOT/PBT)-nanohydroxyapatite (nHA) scaffolds with up to 45 wt% nHA, which presented significantly enhanced compressive mechanical properties, to evaluate their in vitro osteogenic potential as a function of nHA content. While osteogenic gene upregulation and matrix mineralization were observed on all scaffold types when cultured in osteogenic media, human mesenchymal stromal cells did not present an explicitly clear osteogenic phenotype, within the evaluated timeframe, in basic media cultures (i.e. without osteogenic factors). Yet, due to the adsorption of calcium and inorganic phosphate ions from cell culture media and simulated body fluid, the formation of a CaP layer was observed on PEOT/PBT-nHA 45 wt% scaffolds, which is hypothesized to account for their osteoinductivity in the long term in vitro, and osteoconductivity in vivo.

scholarly journals Mesenchymal stromal cells improve human islet function through released products and extracellular matrix

2017 ◽  
Vol 131 (23) ◽  
pp. 2835-2845 ◽  
Author(s):  
Ahmed A. Arzouni ◽  
Andreia Vargas-Seymour ◽  
Chloe L. Rackham ◽  
Paramjeet Dhadda ◽  
Guo-Cai Huang ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Human Islets ◽  
Human Islet ◽  
Human Mscs ◽  
Islet Function ◽  
Secretory Function ◽  
Beneficial Effects

Aims: The aims of the present study were (i) to determine whether the reported beneficial effects of mesenchymal stromal cells (MSCs) on mouse islet function extend to clinically relevant human tissues (islets and MSCs), enabling translation into improved protocols for clinical human islet transplantation; and (ii) to identify possible mechanisms through which human MSCs influence human islet function. Materials and methods: Human islets were co-cultured with human adipose tissue-derived MSCs (hASCs) or pre-treated with its products – extracellular matrix (ECM) and annexin A1 (ANXA1). Mouse islets were pre-treated with mouse MSC-derived ECM. Islet insulin secretory function was assessed in vitro by radioimmunoassay. Quantitative RT-PCR was used to screen human adipMSCs for potential ligands of human islet G-protein-coupled receptors. Results: We show that co-culture with hASCs improves human islet secretory function in vitro, as measured by glucose-stimulated insulin secretion, confirming previous reports using rodent tissues. Furthermore, we demonstrate that these beneficial effects on islet function can be partly attributed to the MSC-derived products ECM and ANXA1. Conclusions: Our results suggest that hASCs have the potential to improve the quality of human islets isolated for transplantation therapy of Type 1 diabetes. Furthermore, it may be possible to achieve improvements in human islet quality in a cell-free culture system by using the MSC-derived products ANXA1 and ECM.

scholarly journals Interleukin-1β Induced Matrix Metalloproteinase Expression in Human Periodontal Ligament-Derived Mesenchymal Stromal Cells under In Vitro Simulated Static Orthodontic Forces

2021 ◽  
Vol 22 (3) ◽  
pp. 1027
Author(s):  
Christian Behm ◽  
Michael Nemec ◽  
Alice Blufstein ◽  
Maria Schubert ◽  
Xiaohui Rausch-Fan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Periodontal Ligament ◽  
Induced Expression ◽  
Gene And Protein Expression ◽  
Tensile Strains ◽  
Orthodontic Forces ◽  
Low Magnitude

The periodontal ligament (PDL) responds to applied orthodontic forces by extracellular matrix (ECM) remodeling, in which human periodontal ligament-derived mesenchymal stromal cells (hPDL-MSCs) are largely involved by producing matrix metalloproteinases (MMPs) and their local inhibitors (TIMPs). Apart from orthodontic forces, the synthesis of MMPs and TIMPs is influenced by the aseptic inflammation occurring during orthodontic treatment. Interleukin (IL)-1β is one of the most abundant inflammatory mediators in this process and crucially affects the expression of MMPs and TIMPs in the presence of cyclic low-magnitude orthodontic tensile forces. In this study we aimed to investigate, for the first time, how IL-1β induced expression of MMPs, TIMPs and how IL-1β in hPDL-MSCs was changed after applying in vitro low-magnitude orthodontic tensile strains in a static application mode. Hence, primary hPDL-MSCs were stimulated with IL-1β in combination with static tensile strains (STS) with 6% elongation. After 6- and 24 h, MMP-1, MMP-2, TIMP-1 and IL-1β expression levels were measured. STS alone had no influence on the basal expression of investigated target genes, whereas IL-1β caused increased expression of these genes. In combination, they increased the gene and protein expression of MMP-1 and the gene expression of MMP-2 after 24 h. After 6 h, STS reduced IL-1β-induced MMP-1 synthesis and MMP-2 gene expression. IL-1β-induced TIMP-1 gene expression was decreased by STS after 6- and 24-h. At both time points, the IL-1β-induced gene expression of IL-1β was increased. Additionally, this study showed that fetal bovine serum (FBS) caused an overall suppression of IL-1β-induced expression of MMP-1, MMP-2 and TIMP-1. Further, it caused lower or opposite effects of STS on IL-1β-induced expression. These observations suggest that low-magnitude orthodontic tensile strains may favor a more inflammatory and destructive response of hPDL-MSCs when using a static application form and that this response is highly influenced by the presence of FBS in vitro.

scholarly journals Growth characteristics of human bone marrow mesenchymal stromal cells at cultivation on synthetic polyelectrolyte nanofilms in vitro

Heliyon ◽  
2021 ◽  
Vol 7 (3) ◽  
pp. e06517
Author(s):  
Lyudmila M. Mezhevikina ◽  
Dmitriy A. Reshetnikov ◽  
Maria G. Fomkina ◽  
Nurbol O. Appazov ◽  
Saltanat Zh. Ibadullayeva ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Growth Characteristics ◽  
Human Bone ◽  
Human Bone Marrow

scholarly journals 3D-printed nerve guidance conduits multi-functionalized with canine multipotent mesenchymal stromal cells promote neuroregeneration after sciatic nerve injury in rats

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Diego Noé Rodríguez-Sánchez ◽  
Giovana Boff Araujo Pinto ◽  
Luciana Politti Cartarozzi ◽  
Alexandre Leite Rodrigues de Oliveira ◽  
Ana Livia Carvalho Bovolato ◽  
...  
Keyword(s):  
Growth Factor ◽  
Sciatic Nerve ◽  
Nerve Injury ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Sciatic Nerve Injury ◽  
Motor Deficits ◽  
3D Printed

Abstract Background Nerve injuries are debilitating, leading to long-term motor deficits. Remyelination and axonal growth are supported and enhanced by growth factor and cytokines. Combination of nerve guidance conduits (NGCs) with adipose-tissue-derived multipotent mesenchymal stromal cells (AdMSCs) has been performing promising strategy for nerve regeneration. Methods 3D-printed polycaprolactone (PCL)-NGCs were fabricated. Wistar rats subjected to critical sciatic nerve damage (12-mm gap) were divided into sham, autograft, PCL (empty NGC), and PCL + MSCs (NGC multi-functionalized with 106 canine AdMSCs embedded in heterologous fibrin biopolymer) groups. In vitro, the cells were characterized and directly stimulated with interferon-gamma to evaluate their neuroregeneration potential. In vivo, the sciatic and tibial functional indices were evaluated for 12 weeks. Gait analysis and nerve conduction velocity were analyzed after 8 and 12 weeks. Morphometric analysis was performed after 8 and 12 weeks following lesion development. Real-time PCR was performed to evaluate the neurotrophic factors BDNF, GDNF, and HGF, and the cytokine and IL-10. Immunohistochemical analysis for the p75NTR neurotrophic receptor, S100, and neurofilament was performed with the sciatic nerve. Results The inflammatory environment in vitro have increased the expression of neurotrophins BDNF, GDNF, HGF, and IL-10 in canine AdMSCs. Nerve guidance conduits multi-functionalized with canine AdMSCs embedded in HFB improved functional motor and electrophysiological recovery compared with PCL group after 12 weeks. However, the results were not significantly different than those obtained using autografts. These findings were associated with a shift in the regeneration process towards the formation of myelinated fibers. Increased immunostaining of BDNF, GDNF, and growth factor receptor p75NTR was associated with the upregulation of BDNF, GDNF, and HGF in the spinal cord of the PCL + MSCs group. A trend demonstrating higher reactivity of Schwann cells and axonal branching in the sciatic nerve was observed, and canine AdMSCs were engrafted at 30 days following repair. Conclusions 3D-printed NGCs multi-functionalized with canine AdMSCs embedded in heterologous fibrin biopolymer as cell scaffold exerted neuroregenerative effects. Our multimodal approach supports the trophic microenvironment, resulting in a pro-regenerative state after critical sciatic nerve injury in rats.

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