Therapeutic efficiency of bone marrow-derived mesenchymal stem cells for liver fibrosis: A systematic review of in vivo studies

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.

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Human Menstrual Blood-Derived Mesenchymal Stem Cells as Potential Cell Carriers for Oncolytic Adenovirus

Stem Cells International ◽

10.1155/2017/3615729 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 11

Author(s):

R. Moreno ◽

L. A. Rojas ◽

Felip Vilardell Villellas ◽

Vanessa Cervera Soriano ◽

J. García-Castro ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

In Vivo Studies ◽

Menstrual Blood ◽

Alternative Source ◽

Regional Administration ◽

Cell Carriers

Antitumor efficacy of systemically administered oncolytic adenoviruses (OAdv) is limited due to diverse factors such as liver sequestration, neutralizing interactions in blood, elimination by the immune system, and physical barriers in tumors. It is therefore of clinical relevance to improve OAdv bioavailability and tumor delivery. Among the variety of tumor-targeting strategies, the use of stem cells and specifically bone marrow-derived mesenchymal stem cells (BM-MSCs) is of particular interest due to their tumor tropism and immunomodulatory properties. Nonetheless, the invasive methods to obtain these cells, the low number of MSCs present in the bone marrow, and their restricted in vitro expansion represent major obstacles for their use in cancer treatments, pointing out the necessity to identify an alternative source of MSCs. Here, we have evaluated the use of menstrual blood-derived mesenchymal stem cells (MenSCs) as cell carriers for regional delivery of an OAdv in the tumor. Our results indicate that MenSCs can be isolated without invasive methods, they have an increased proliferation rate compared to BM-MSCs, and they can be efficiently infected with different serotype 5-based capsid-modified adenoviruses, leading to viral replication and release. In addition, our in vivo studies confirmed the tumor-homing properties of MenSCs after regional administration.

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Potential of Fibrin Glue and Mesenchymal Stem Cells (MSCs) to Regenerate Nerve Injuries: A Systematic Review

Cells ◽

10.3390/cells11020221 ◽

2022 ◽

Vol 11 (2) ◽

pp. 221

Author(s):

Adriana de Cássia Ortiz ◽

Simone Ortiz Moura Fideles ◽

Karina Torres Pomini ◽

Márcia Zilioli Bellini ◽

Eliana de Souza Bastos Mazuqueli Pereira ◽

...

Keyword(s):

Systematic Review ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Nerve Regeneration ◽

Fibrin Glue ◽

Nerve Fibers ◽

In Vivo Studies ◽

Eligibility Criteria ◽

Cell Based Therapy

Cell-based therapy is a promising treatment to favor tissue healing through less invasive strategies. Mesenchymal stem cells (MSCs) highlighted as potential candidates due to their angiogenic, anti-apoptotic and immunomodulatory properties, in addition to their ability to differentiate into several specialized cell lines. Cells can be carried through a biological delivery system, such as fibrin glue, which acts as a temporary matrix that favors cell-matrix interactions and allows local and paracrine functions of MSCs. Thus, the aim of this systematic review was to evaluate the potential of fibrin glue combined with MSCs in nerve regeneration. The bibliographic search was performed in the PubMed/MEDLINE, Web of Science and Embase databases, using the descriptors (“fibrin sealant” OR “fibrin glue”) AND “stem cells” AND “nerve regeneration”, considering articles published until 2021. To compose this review, 13 in vivo studies were selected, according to the eligibility criteria. MSCs favored axonal regeneration, remyelination of nerve fibers, as well as promoted an increase in the number of myelinated fibers, myelin sheath thickness, number of axons and expression of growth factors, with significant improvement in motor function recovery. This systematic review showed clear evidence that fibrin glue combined with MSCs has the potential to regenerate nervous system lesions.

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

Stem Cell Research & Therapy ◽

10.1186/s13287-020-02110-x ◽

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.

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Hydrogen alleviates cellular senescence via regulation of ROS/p53/p21 pathway in bone marrow-derived mesenchymal stem cells in vivo

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2018.07.020 ◽

2018 ◽

Vol 106 ◽

pp. 1126-1134 ◽

Cited By ~ 3

Author(s):

Wenbo Zhang ◽

Chao Huang ◽

Aijun Sun ◽

Liang Qiao ◽

Xi Zhang ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Cellular Senescence

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The Dynamic in vivo Distribution of Bone Marrow-Derived Mesenchymal Stem Cells after Infusion

Cells Tissues Organs ◽

10.1159/000047856 ◽

2001 ◽

Vol 169 (1) ◽

pp. 12-20 ◽

Cited By ~ 609

Author(s):

Jizong Gao ◽

James E. Dennis ◽

Raymond F. Muzic ◽

Magnus Lundberg ◽

Arnold I. Caplan

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

In Vivo Distribution

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Mesenchymal Stem Cells and Induced Bone Marrow-Derived Macrophages Synergistically Improve Liver Fibrosis in Mice

Stem Cells Translational Medicine ◽

10.1002/sctm.18-0105 ◽

2018 ◽

Vol 8 (3) ◽

pp. 271-284 ◽

Cited By ~ 26

Author(s):

Yusuke Watanabe ◽

Atsunori Tsuchiya ◽

Satoshi Seino ◽

Yuzo Kawata ◽

Yuichi Kojima ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Liver Fibrosis

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

Biomaterials Science ◽

10.1039/c8bm00846a ◽

2019 ◽

Vol 7 (1) ◽

pp. 362-372 ◽

Cited By ~ 6

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.

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The Efficacy of Stem Cells Secretome Application in Osteoarthritis: A Systematic Review of In Vivo Studies

Stem Cell Reviews and Reports ◽

10.1007/s12015-020-09980-x ◽

2020 ◽

Vol 16 (6) ◽

pp. 1222-1241 ◽

Cited By ~ 1

Author(s):

Maria Bousnaki ◽

Athina Bakopoulou ◽

Aristeidis Kritis ◽

Petros Koidis

Keyword(s):

Systematic Review ◽

Stem Cells ◽

In Vivo Studies

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BMAC and Adipose-Derived MSCs Treatment for Knee Osteoarthritis: A Systematic Review

International Journal of Clinical Case Reports and Reviews ◽

10.31579/2690-4861/150 ◽

2021 ◽

Vol 7 (04) ◽

pp. 01-11

Author(s):

Pooja Pithadia

Keyword(s):

Systematic Review ◽

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Knee Osteoarthritis ◽

Bone Marrow Aspirate ◽

Stromal Vascular Fraction ◽

Cochrane Library ◽

Bone Marrow Aspirate Concentrate ◽

Mesh Terms

Background: Knee osteoarthritis is the most common musculoskeletal progressive disorder that affects nearly 303 million people worldwide. This condition prevails in 10% males and 13% females among the elders above 60. Although there is conventional nonsurgical and surgical treatment available for knee osteoarthritis, there is a fascinating interest in bone marrow aspirate concentrate (BMAC) as well as adipose-derived mesenchymal stem cells (AD-MSC), including enzymatically treated stromal vascular fraction (SVF) and mechanically treated (microfat/nanofat) injections among physicians. Hence, this systematic review aims to determine the efficacy of BMAC and AD-MSCs (enzyme and mechanically treated) injections for knee osteoarthritis treatment. Methods: A systematic review was performed on the following data sources (PubMed, Scopus, Google Scholar, EMBASE, and Cochrane Library) published on March 31, 2021. The keywords or MeSH terms include 'Knee Osteoarthritis with 'Bone marrow aspirate concentrate' OR 'BMAC' or with 'Adipose-derived mesenchymal stem cells (AD-MSC)' or with 'Stromal vascular fraction' OR 'SVF' or 'Mechanically treated AD-MSC (mfat/nanofat)'. In addition, the retrieved articles were further reviewed to identify relevant research studies. Results: The authors reviewed and tabulated data based on the year of study, study type, therapy protocol, patient population, outcome measures, and interpretation. Among the 382 records screened, 43 studies (16 on BMAC and 27 on AD-MSCs) were included in the systematic review study. Among them, only 5 were randomized controlled trials. These selected studies demonstrated short-term positive outcomes such as improvement in knee pain and function with no adverse side effects. Moreover, researchers reported varied administration methods of BMAC or AD-MSC either as standalone or in combination with other conservative procedures such as PRP (Platelets Rich Plasma), HA (Hyaluronic acid), or surgery. Conclusions: BMAC and AD-MSC (enzymatically and mechanically treated) injections prove safer and more efficacious in patients with knee osteoarthritis for a shorter duration of 2 years. However, the available literature lacks high-quality studies with no varied clinical settings and long-term follow-up of more than two years.

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