scholarly journals Human Fetal Bone Marrow-Derived Mesenchymal Stem Cells Promote the Proliferation and Differentiation of Pancreatic Progenitor Cells and the Engraftment Function of Islet-Like Cell Clusters

2019 ◽  
Vol 20 (17) ◽  
pp. 4083
Author(s):  
Xing Yu Li ◽  
Shang Ying Wu ◽  
Po Sing Leung
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Progenitor Cells ◽  
Pancreatic Progenitor ◽  
Pancreatic Progenitor Cells ◽  
Proliferation And Differentiation ◽  
Differentiation And Proliferation

Pancreatic progenitor cells (PPCs) are the primary source for all pancreatic cells, including beta-cells, and thus the proliferation and differentiation of PPCs into islet-like cell clusters (ICCs) opens an avenue to providing transplantable islets for diabetic patients. Meanwhile, mesenchymal stem cells (MSCs) can enhance the development and function of different cell types of interest, but their role on PPCs remains unknown. We aimed to explore the mechanism-of-action whereby MSCs induce the in vitro and in vivo PPC/ICC development by means of our established co-culture system of human PPCs with human fetal bone marrow-derived MSCs. We examined the effect of MSC-conditioned medium on PPC proliferation and survival. Meanwhile, we studied the effect of MSC co-culture enhanced PPC/ICC function in vitro and in vivo co-/transplantation. Furthermore, we identified IGF1 as a critical factor responsible for the MSC effects on PPC differentiation and proliferation via IGF1-PI3K/Akt and IGF1-MEK/ERK1/2, respectively. In conclusion, our data indicate that MSCs stimulated the differentiation and proliferation of human PPCs via IGF1 signaling, and more importantly, promoted the in vivo engraftment function of ICCs. Taken together, our protocol may provide a mechanism-driven basis for the proliferation and differentiation of PPCs into clinically transplantable islets.

scholarly journals Comparative analysis of mouse bone marrow and adipose tissue mesenchymal stem cells for critical limb ischemia cell therapy

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pegah Nammian ◽  
Seyedeh-Leili Asadi-Yousefabad ◽  
Sajad Daneshi ◽  
Mohammad Hasan Sheikhha ◽  
Seyed Mohammad Bagher Tabei ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Cell Therapy ◽  
Femoral Artery ◽  
Critical Limb Ischemia ◽  
Limb Ischemia

Abstract Introduction Critical limb ischemia (CLI) is the most advanced form of peripheral arterial disease (PAD) characterized by ischemic rest pain and non-healing ulcers. Currently, the standard therapy for CLI is the surgical reconstruction and endovascular therapy or limb amputation for patients with no treatment options. Neovasculogenesis induced by mesenchymal stem cells (MSCs) therapy is a promising approach to improve CLI. Owing to their angiogenic and immunomodulatory potential, MSCs are perfect candidates for the treatment of CLI. The purpose of this study was to determine and compare the in vitro and in vivo effects of allogeneic bone marrow mesenchymal stem cells (BM-MSCs) and adipose tissue mesenchymal stem cells (AT-MSCs) on CLI treatment. Methods For the first step, BM-MSCs and AT-MSCs were isolated and characterized for the characteristic MSC phenotypes. Then, femoral artery ligation and total excision of the femoral artery were performed on C57BL/6 mice to create a CLI model. The cells were evaluated for their in vitro and in vivo biological characteristics for CLI cell therapy. In order to determine these characteristics, the following tests were performed: morphology, flow cytometry, differentiation to osteocyte and adipocyte, wound healing assay, and behavioral tests including Tarlov, Ischemia, Modified ischemia, Function and the grade of limb necrosis scores, donor cell survival assay, and histological analysis. Results Our cellular and functional tests indicated that during 28 days after cell transplantation, BM-MSCs had a great effect on endothelial cell migration, muscle restructure, functional improvements, and neovascularization in ischemic tissues compared with AT-MSCs and control groups. Conclusions Allogeneic BM-MSC transplantation resulted in a more effective recovery from critical limb ischemia compared to AT-MSCs transplantation. In fact, BM-MSC transplantation could be considered as a promising therapy for diseases with insufficient angiogenesis including hindlimb ischemia.

Inner ear progenitor cells can be generated in vitro from human bone marrow mesenchymal stem cells

2012 ◽  
Vol 7 (6) ◽  
pp. 757-767 ◽  
Author(s):  
Sarah L Boddy ◽  
Wei Chen ◽  
Ricardo Romero-Guevara ◽  
Lucksy Kottam ◽  
Illaria Bellantuono ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Inner Ear ◽  
Progenitor Cells ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Marrow Mesenchymal Stem Cells

scholarly journals Mechanism of Action of Diallyl Sulphide in Ameliorating the Hematopoietic Radiation Injury

2021 ◽  
Author(s):  
Omika Katoch ◽  
Mrinalini Tiwari ◽  
Namita Kalra ◽  
Paban K. Agrawala
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Progenitor Cells ◽  
Hematopoietic Stem ◽  
Proliferation And Differentiation ◽  
Stem And Progenitor Cells ◽  
Radiation Induced ◽  
Medicinal Properties ◽  
Marrow Cellularity

AbstractDiallyl sulphide (DAS), the pungent component of garlic, is known to have several medicinal properties and has recently been shown to have radiomitigative properties. The present study was performed to better understand its mode of action in rendering radiomitigation. Evaluation of the colonogenic ability of hematopoietic progenitor cells (HPCs) on methocult media, proliferation and differentiation of hematopoietic stem cells (HSCs), and transplantation of stem cells were performed. The supporting tissue of HSCs was also evaluated by examining the histology of bone marrow and in vitro colony-forming unit–fibroblast (CFU-F) count. Alterations in the levels of IL-5, IL-6 and COX-2 were studied as a function of radiation or DAS treatment. It was observed that an increase in proliferation and differentiation of hematopoietic stem and progenitor cells occurred by postirradiation DAS administration. It also resulted in increased circulating and bone marrow homing of transplanted stem cells. Enhancement in bone marrow cellularity, CFU-F count, and cytokine IL-5 level were also evident. All those actions of DAS that could possibly add to its radiomitigative potential and can be attributed to its HDAC inhibitory properties, as was observed by the reversal radiation induced increase in histone acetylation.

Recombinant human BMP-2 accelerates the migration of bone marrow mesenchymal stem cells via the CDC42/PAK1/LIMK1 pathway in vitro and in vivo

2019 ◽  
Vol 7 (1) ◽  
pp. 362-372 ◽  
Author(s):  
Shuhao Liu ◽  
Yang Liu ◽  
Libo Jiang ◽  
Zheng Li ◽  
Soomin Lee ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Marrow Mesenchymal Stem Cells

BMP-2-induced migration of BMSCs can be inhibited by silencing CDC42 in vitro and in vivo.

scholarly journals Melatonin Inhibits the Ferroptotic Pathway in Rat Bone Marrow Mesenchymal Stem Cells by Activating the PI3K-AKT-mTOR Signaling Axis to Attenuate Steroid-induced Osteoporosis

2021 ◽  
Author(s):  
meng li ◽  
ning yang ◽  
li hao ◽  
wei zhou ◽  
lei li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Signaling ◽  
High Dose ◽  
Treatment Pathways ◽  
Marrow Mesenchymal Stem Cells

Abstract ObjectivesSteroid-induced osteoporosis (SIOP) is a secondary osteoporosis, which is a systemic bone disease characterized by low bone mass, bone microstructure damage, increased bone fragility, and easy fracture. However, the specific mechanism remains unclear. Glucocorticoid-induced death of osteoblasts and bone marrow mesenchymal stem cells (BMSCs) is an important factor in SIOP. Ferroptosis is an iron-dependent programmed cell death that differs from apoptosis, cell necrosis, and autophagy, which can be induced by many factors. Herein, we aimed to explore whether glucocorticoids (GCs) cause ferroptosis in BMSCs and determine possible treatment pathways and mechanisms of action. Melatonin (MT), a hormone secreted by the pineal gland, displays strong antioxidant abilities to scavenge free radicals and alleviates ferroptosis in many tissues and organs. MethodsIn this study, we used high-dose dexamethasone (DEX) to observe whether glucocorticoids induced ferroptosis in BMSCs. We then assessed whether MT can inhibit the ferroptotic pathway, thereby providing early protection against GC-induced SIOP, and investigated the signaling pathways involved.ResultsIn vitro experiments showed that MT intervention significantly improved GC-induced ferroptosis in BMSCs and significantly improved SIOP in vivo. Pathway analysis showed that MT improves ferroptosis by activating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) axis. MT upregulates expression of PI3K, which is an important regulator of ferroptosis resistance. PI3K activators mimic the anti-ferroptosis effect of MT, but after blocking the PI3K pathway, the effect of MT is weakened. Obviously, MT can protect against SIOP induced by GC. Notably, even after GC-induced ferroptosis begins, MT can confer protection against SIOP. ConclusionOur research confirms that GC-induced ferroptosis is closely related to SIOP. Melatonin can inhibit ferroptosis by activating the PI3K-AKT-mTOR signaling pathway, thereby reducing the occurrence of steroid-induced osteoporosis. Therefore, MT may provide a novel strategy for preventing and treating SIOP.

In vivo and in vitro study of osteogenic potency of endothelin-1 on bone marrow-derived mesenchymal stem cells

2017 ◽  
Vol 357 (1) ◽  
pp. 25-32 ◽  
Author(s):  
Long-Wei Hu ◽  
Xiao Wang ◽  
Xin-Qun Jiang ◽  
Li-Qun Xu ◽  
Hong-Ya Pan
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
In Vitro Study ◽  
Vitro Study ◽  
Endothelin 1

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.

The negatively charged microenvironment of collagen hydrogels regulates the chondrogenic differentiation of bone marrow mesenchymal stem cells in vitro and in vivo

2020 ◽  
Vol 8 (21) ◽  
pp. 4680-4693
Author(s):  
Jirong Yang ◽  
Yumei Xiao ◽  
Zizhao Tang ◽  
Zhaocong Luo ◽  
Dongxiao Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Protein Adsorption ◽  
Cell Morphology ◽  
Chondrogenic Differentiation ◽  
Collagen Hydrogels ◽  
Marrow Mesenchymal Stem Cells

The different negatively charged microenvironments of collagen hydrogels affect the protein adsorption, cell morphology, and chondrogenic differentiation of BMSCs in vitro and in vivo.

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