scholarly journals Cartilaginous and osteochondral tissue formation by human mesenchymal stem cells on three-dimensionally woven scaffolds

2018 ◽  
Author(s):  
Benjamin L. Larson ◽  
Sarah N. Yu ◽  
Hyoungshin Park ◽  
Bradley T. Estes ◽  
Franklin T. Moutos ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Expression Profiles ◽  
Human Mesenchymal Stem Cells ◽  
Paracrine Factors ◽  
Nude Rat ◽  
Adult Human ◽  
Osteochondral Repair

AbstractThe development of mechanically functional cartilage and bone tissue constructs of clinically relevant size, as well as their integration with native tissues, remain important challenges for regenerative medicine. The objective of this study was to assess adult human mesenchymal stem cells (MSC) in large, three dimensionally woven poly(ε-caprolactone) (PCL) scaffolds in proximity to viable bone, both in a nude rat subcutaneous pouch model and under simulated conditions in vitro. In Study I, various scaffold permutations: PCL alone, PCL-bone, “point-of- care” seeded MSC-PCL-bone, and chondrogenically pre-cultured Ch-MSC-PCL-bone constructs were implanted in a dorsal, ectopic pouch in a nude rat. After eight weeks, only cells in the Ch- MSC-PCL constructs exhibited both chondrogenic and osteogenic gene expression profiles. Notably, while both tissue profiles were present, constructs that had been chondrogenically pre- cultured prior to implantation showed a loss of glycosaminoglycan (GAG) as well as the presence of mineralization along with the formation of trabecula-like structures. In Study II of the study, the GAG loss and mineralization observed in Study I in vivo were recapitulated in vitro by the presence of either nearby bone or osteogenic culture medium additives but were prevented by a continued presence of chondrogenic medium additives. These data suggest conditions under which adult human stem cells in combination with polymer scaffolds synthesize functional and phenotypically distinct tissues based on the environmental conditions, and highlight the potential influence that paracrine factors from adjacent bone may have on MSC fate, once implanted in vivo for chondral or osteochondral repair.

scholarly journals Adropin-based dual treatment enhances the therapeutic potential of mesenchymal stem cells in rat myocardial infarction

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
HuiYa Li ◽  
DanQing Hu ◽  
Guilin Chen ◽  
DeDong Zheng ◽  
ShuMei Li ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Potential ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Paracrine Factors ◽  
Dual Treatment

AbstractBoth weak survival ability of stem cells and hostile microenvironment are dual dilemma for cell therapy. Adropin, a bioactive substance, has been demonstrated to be cytoprotective. We therefore hypothesized that adropin may produce dual protective effects on the therapeutic potential of stem cells in myocardial infarction by employing an adropin-based dual treatment of promoting stem cell survival in vitro and modifying microenvironment in vivo. In the current study, adropin (25 ng/ml) in vitro reduced hydrogen peroxide-induced apoptosis in rat bone marrow mesenchymal stem cells (MSCs) and improved MSCs survival with increased phosphorylation of Akt and extracellular regulated protein kinases (ERK) l/2. Adropin-induced cytoprotection was blocked by the inhibitors of Akt and ERK1/2. The left main coronary artery of rats was ligated for 3 or 28 days to induce myocardial infarction. Bromodeoxyuridine (BrdU)-labeled MSCs, which were in vitro pretreated with adropin, were in vivo intramyocardially injected after ischemia, following an intravenous injection of 0.2 mg/kg adropin (dual treatment). Compared with MSCs transplantation alone, the dual treatment with adropin reported a higher level of interleukin-10, a lower level of tumor necrosis factor-α and interleukin-1β in plasma at day 3, and higher left ventricular ejection fraction and expression of paracrine factors at day 28, with less myocardial fibrosis and higher capillary density, and produced more surviving BrdU-positive cells at day 3 and 28. In conclusion, our data evidence that adropin-based dual treatment may enhance the therapeutic potential of MSCs to repair myocardium through paracrine mechanism via the pro-survival pathways.

Characterization of patient-derived bone marrow human mesenchymal stem cells as oncolytic virus carriers for the treatment of glioblastoma

2021 ◽  
pp. 1-11
Author(s):  
Yuzaburo Shimizu ◽  
Joy Gumin ◽  
Feng Gao ◽  
Anwar Hossain ◽  
Elizabeth J. Shpall ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cells ◽  
Oncolytic Viruses ◽  
In Vivo Studies ◽  
Systemic Delivery ◽  
Previously Treated

OBJECTIVE Delta-24-RGD is an oncolytic adenovirus that is capable of replicating in and killing human glioma cells. Although intratumoral delivery of Delta-24-RGD can be effective, systemic delivery would improve its clinical application. Bone marrow–derived human mesenchymal stem cells (BM-hMSCs) obtained from healthy donors have been investigated as virus carriers. However, it is unclear whether BM-hMSCs can be derived from glioma patients previously treated with marrow-toxic chemotherapy or whether such BM-hMSCs can deliver oncolytic viruses effectively. Herein, the authors undertook a prospective clinical trial to determine the feasibility of obtaining BM-hMSCs from patients with recurrent malignant glioma who were previously exposed to marrow-toxic chemotherapy. METHODS The authors enrolled 5 consecutive patients who had been treated with radiation therapy and chemotherapy. BM aspirates were obtained from the iliac crest and were cultured to obtain BM-hMSCs. RESULTS The patient-derived BM-hMSCs (PD-BM-hMSCs) had a morphology similar to that of healthy donor–derived BM-hMSCs (HD-BM-hMSCs). Flow cytometry revealed that all 5 cell lines expressed canonical MSC surface markers. Importantly, these cultures could be made to differentiate into osteocytes, adipocytes, and chondrocytes. In all cases, the PD-BM-hMSCs homed to intracranial glioma xenografts in mice after intracarotid delivery as effectively as HD-BM-hMSCs. The PD-BM-hMSCs loaded with Delta-24-RGD (PD-BM-MSC-D24) effectively eradicated human gliomas in vitro. In in vivo studies, intravascular administration of PD-BM-MSC-D24 increased the survival of mice harboring U87MG gliomas. CONCLUSIONS The authors conclude that BM-hMSCs can be acquired from patients previously treated with marrow-toxic chemotherapy and that these PD-BM-hMSCs are effective carriers for oncolytic viruses.

Effects of a bone-like mineral film on phenotype of adult human mesenchymal stem cells in vitro

Biomaterials ◽  
2005 ◽  
Vol 26 (3) ◽  
pp. 303-310 ◽  
Author(s):  
W MURPHY ◽  
S HSIONG ◽  
T RICHARDSON ◽  
C SIMMONS ◽  
D MOONEY
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cells ◽  
Adult Human

scholarly journals Canonical Wnts function as potent regulators of osteogenesis by human mesenchymal stem cells

2009 ◽  
Vol 185 (1) ◽  
pp. 67-75 ◽  
Author(s):  
Guizhong Liu ◽  
Sapna Vijayakumar ◽  
Luca Grumolato ◽  
Randy Arroyave ◽  
HuiFang Qiao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Formation ◽  
Wnt Signaling ◽  
De Novo ◽  
Human Mesenchymal Stem Cells ◽  
Mitogen Activated Protein Kinase ◽  
Bone Homeostasis

Genetic evidence indicates that Wnt signaling is critically involved in bone homeostasis. In this study, we investigated the functions of canonical Wnts on differentiation of adult multipotent human mesenchymal stem cells (hMSCs) in vitro and in vivo. We observe differential sensitivities of hMSCs to Wnt inhibition of osteogenesis versus adipogenesis, which favors osteoblastic commitment under binary in vitro differentiation conditions. Wnt inhibition of osteogenesis is associated with decreased expression of osteoblastic transcription factors and inhibition of c-Jun N-terminal kinase and p38 mitogen-activated protein kinase activation, which are involved in osteogenic differentiation. An hMSC subpopulation exhibits high endogenous Wnt signaling, the inhibition of which enhances osteogenic and adipogenic differentiation in vitro. In an in vivo bone formation model, high levels of Wnt signaling inhibit de novo bone formation by hMSCs. However, hMSCs with exogenous expression of Wnt1 but not stabilized β-catenin markedly stimulate bone formation by naive hMSCs, arguing for an important role of a canonical Wnt gradient in hMSC osteogenesis in vivo.

scholarly journals Dilution of human mesenchymal stem cells with dermal fibroblasts and the effects on in vitro and in vivo osteochondrogenesis

2000 ◽  
Vol 219 (1) ◽  
pp. 50-62 ◽  
Author(s):  
Donald P. Lennon ◽  
Stephen E. Haynesworth ◽  
Douglas M. Arm ◽  
Marilyn A. Baber ◽  
Arnold I. Caplan
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cells ◽  
Dermal Fibroblasts

Impact of Indium-111 Oxine Labelling on Viability of Human Mesenchymal Stem Cells In Vitro, and 3D Cell-Tracking Using SPECT/CT In Vivo

2010 ◽  
Vol 13 (6) ◽  
pp. 1204-1214 ◽  
Author(s):  
Franz Josef Gildehaus ◽  
Florian Haasters ◽  
Inga Drosse ◽  
Erika Wagner ◽  
Christian Zach ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Tracking ◽  
Human Mesenchymal Stem Cells ◽  
Indium 111

Paracrine factors of human mesenchymal stem cells increase wound closure and reduce reactive oxygen species production in a traumatic brain injury in vitro model

2013 ◽  
Vol 33 (7) ◽  
pp. 673-684 ◽  
Author(s):  
D Torrente ◽  
MF Avila ◽  
R Cabezas ◽  
L Morales ◽  
J Gonzalez ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Brain Injury ◽  
Wound Closure ◽  
Human Mesenchymal Stem Cells ◽  
Neuronal Population ◽  
Paracrine Factors ◽  
Neuroprotective Strategy

Traumatic brain injury (TBI) consists of a primary and a secondary insult characterized by a biochemical cascade that plays a crucial role in cell death in the brain. Despite the major improvements in the acute care of head injury victims, no effective strategies exist for preventing the secondary injury cascade. This lack of success might be due to that most treatments are aimed at targeting neuronal population, even if studies show that astrocytes play a key role after a brain damage. In this work, we propose a new model of in vitro traumatic brain-like injury and use paracrine factors released by human mesenchymal stem cells (hMSCs) as a neuroprotective strategy. Our results demonstrate that hMSC-conditioned medium increased wound closure and proliferation at 12 h and reduced superoxide production to control conditions. This was accompanied by changes in cell morphology and polarity index, as both parameters reflect the ability of cells to migrate toward the wound. These findings indicate that hMSC is an important regulator of oxidative stress production, enhances cells migration, and shall be considered as a useful neuroprotective approach for brain recovery following injury.

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