Behavior of Mesenchymal Stem Cells Obtained From Dental Tissues: A Review of the Literature

The success of tissue engineering in combination with tissue regeneration depends on the behavior and cellular activity in the biological processes developed within a structure that functions as a support, better known as scaffolds, or directly at the site of the injury. The cell-cell and cell-biomaterial interaction are key factors for the induction of a specific cell behavior, together with the bioactive factors that allow the formation of the desired tissue. Mesenchymal Stem Cells (MSC) can be isolated from the umbilical cord and bone marrow; however, the behavior of Dental Pulp Stem Cells (DPSC) has been shown to have a high potential for the formation of bone tissue, and these cells have even been able to induce the process of angiogenesis. Advances in periodontal regeneration, dentin-pulp complex, and craniofacial bone defects through the induction of MSC obtained from tooth structures in in vitro-in vivo studies have permitted the obtaining of clinical evidence of the achievements obtained to date.

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

Journal of Neurosurgery ◽

10.3171/2021.3.jns203045 ◽

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.

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Research Status of Mesenchymal Stem Cells in Liver Transplantation

Cell Transplantation ◽

10.1177/0963689719874786 ◽

2019 ◽

Vol 28 (12) ◽

pp. 1490-1506 ◽

Cited By ~ 2

Author(s):

Yu You ◽

Di-guang Wen ◽

Jian-ping Gong ◽

Zuo-jin Liu

Keyword(s):

Stem Cells ◽

Liver Transplantation ◽

Clinical Trials ◽

Mesenchymal Stem Cells ◽

In Vivo Studies ◽

Cell Contact ◽

Clinical Effects ◽

Clinical Safety

Liver transplantation has been deemed the best choice for end-stage liver disease patients but immune rejection after surgery is still a serious problem. Patients have to take immunosuppressive drugs for a long time after liver transplantation, and this often leads to many side effects. Mesenchymal stem cells (MSCs) gradually became of interest to researchers because of their powerful immunomodulatory effects. In the past, a large number of in vitro and in vivo studies have demonstrated the great potential of MSCs for participation in posttransplant immunomodulation. In addition, MSCs also have properties that may potentially benefit patients undergoing liver transplantation. This article aims to provide an overview of the current understanding of the immunomodulation achieved by the application of MSCs in liver transplantation, to discuss the problems that may be encountered when using MSCs in clinical practice, and to describe some of the underlying capabilities of MSCs in liver transplantation. Cell–cell contact, soluble molecules, and exosomes have been suggested to be critical approaches to MSCs’ immunoregulation in vitro; however, the exact mechanism, especially in vivo, is still unclear. In recent years, the clinical safety of MSCs has been proven by a series of clinical trials. The obstacles to the clinical application of MSCs are decreasing, but large sample clinical trials involving MSCs are still needed to further study their clinical effects.

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Combined effects of multi-scale topographical cues on stable cell sheet formation and differentiation of mesenchymal stem cells

Biomaterials Science ◽

10.1039/c7bm00134g ◽

2017 ◽

Vol 5 (10) ◽

pp. 2056-2067 ◽

Cited By ~ 6

Author(s):

Sisi Li ◽

Shreyas Kuddannaya ◽

Yon Jin Chuah ◽

Jingnan Bao ◽

Yilei Zhang ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Cell Sheet ◽

Specific Cell ◽

Combined Effects ◽

Multi Scale ◽

Cell Responses ◽

Topographical Cues

To decipher specific cell responses to diverse and complex in vivo signals, it is essential to emulate specific surface chemicals, extra cellular matrix (ECM) components and topographical signals through reliable and easily reproducible in vitro systems.

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Anti-Inflammatory Fibronectin-AgNP for Regulation of Biological Performance and Endothelial Differentiation Ability of Mesenchymal Stem Cells

International Journal of Molecular Sciences ◽

10.3390/ijms22179262 ◽

2021 ◽

Vol 22 (17) ◽

pp. 9262

Author(s):

Huey-Shan Hung ◽

Kai-Bo Chang ◽

Cheng-Ming Tang ◽

Tian-Ren Ku ◽

Mei-Lang Kung ◽

...

Keyword(s):

Stem Cells ◽

Immune Response ◽

Silver Nanoparticles ◽

Mesenchymal Stem Cells ◽

Superior Performance ◽

In Vivo Studies ◽

Vascular Regeneration ◽

Anti Inflammatory

The engineering of vascular regeneration still involves barriers that need to be conquered. In the current study, a novel nanocomposite comprising of fibronectin (denoted as FN) and a small amount of silver nanoparticles (AgNP, ~15.1, ~30.2 or ~75.5 ppm) was developed and its biological function and biocompatibility in Wharton’s jelly-derived mesenchymal stem cells (MSCs) and rat models was investigated. The surface morphology as well as chemical composition for pure FN and the FN-AgNP nanocomposites incorporating various amounts of AgNP were firstly characterized by atomic force microscopy (AFM), UV-Visible spectroscopy (UV-Vis), and Fourier-transform infrared spectroscopy (FTIR). Among the nanocomposites, FN-AgNP with 30.2 ppm silver nanoparticles demonstrated the best biocompatibility as assessed through intracellular ROS production, proliferation of MSCs, and monocytes activation. The expression levels of pro-inflammatory cytokines, TNF-α, IL-1β, and IL-6, were also examined. FN-AgNP 30.2 ppm significantly inhibited pro-inflammatory cytokine expression compared to other materials, indicating superior performance of anti-immune response. Mechanistically, FN-AgNP 30.2 ppm significantly induced greater expression of vascular endothelial growth factor (VEGF) and stromal-cell derived factor-1 alpha (SDF-1α) and promoted the migration of MSCs through matrix metalloproteinase (MMP) signaling pathway. Besides, in vitro and in vivo studies indicated that FN-AgNP 30.2 ppm stimulated greater protein expressions of CD31 and von Willebrand Factor (vWF) as well as facilitated better endothelialization capacity than other materials. Furthermore, the histological tissue examination revealed the lowest capsule formation and collagen deposition in rat subcutaneous implantation of FN-AgNP 30.2 ppm. In conclusion, FN-AgNP nanocomposites may facilitate the migration and proliferation of MSCs, induce endothelial cell differentiation, and attenuate immune response. These finding also suggests that FN-AgNP may be a potential anti-inflammatory surface modification strategy for vascular biomaterials.

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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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Pharmacokinetic—Pharmacodynamic Modeling of Tumor Targeted Drug Delivery Using Nano-Engineered Mesenchymal Stem Cells

Pharmaceutics ◽

10.3390/pharmaceutics13010092 ◽

2021 ◽

Vol 13 (1) ◽

pp. 92

Author(s):

Shen Cheng ◽

Susheel Kumar Nethi ◽

Mahmoud Al-Kofahi ◽

Swayam Prabha

Keyword(s):

Drug Delivery ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Targeted Drug Delivery ◽

Quantitative Description ◽

In Vivo Studies ◽

Pharmacodynamic Modeling ◽

Targeted Drug

Nano-engineered mesenchymal stem cells (nano-MSCs) are promising targeted drug delivery platforms for treating solid tumors. MSCs engineered with paclitaxel (PTX) loaded poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) are efficacious in treating lung and ovarian tumors in mouse models. The quantitative description of pharmacokinetics (PK) and pharmacodynamics (PD) of nano-MSCs is crucial for optimizing their therapeutic efficacy and clinical translatability. However, successful translation of nano-MSCs is challenging due to their complex composition and physiological mechanisms regulating their pharmacokinetic-pharmacodynamic relationship (PK–PD). Therefore, in this study, a mechanism-based preclinical PK–PD model was developed to characterize the PK–PD relationship of nano-MSCs in orthotopic A549 human lung tumors in SCID Beige mice. The developed model leveraged literature information on diffusivity and permeability of PTX and PLGA NPs, PTX release from PLGA NPs, exocytosis of NPs from MSCs as well as PK and PD profiles of nano-MSCs from previous in vitro and in vivo studies. The developed PK–PD model closely captured the reported tumor growth in animals receiving no treatment, PTX solution, PTX-PLGA NPs and nano-MSCs. Model simulations suggest that increasing the dosage of nano-MSCs and/or reducing the rate of PTX-PLGA NPs exocytosis from MSCs could result in improved anti-tumor efficacy in preclinical settings.

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Mesenchymal Stem Cells Empowering Tendon Regenerative Therapies

International Journal of Molecular Sciences ◽

10.3390/ijms20123002 ◽

2019 ◽

Vol 20 (12) ◽

pp. 3002 ◽

Cited By ~ 18

Author(s):

Raquel Costa-Almeida ◽

Isabel Calejo ◽

Manuela E. Gomes

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Tendon Repair ◽

Tendon Healing ◽

In Vivo Studies ◽

Competent Cell ◽

Tendon Regeneration ◽

Regenerative Therapies

Tendon tissues have limited healing capacity. The incidence of tendon injuries and the unsatisfactory functional outcomes of tendon repair are driving the search for alternative therapeutic approaches envisioning tendon regeneration. Cellular therapies aim at delivering adequate, regeneration-competent cell types to the injured tendon and toward ultimately promoting its reconstruction and recovery of functionality. Mesenchymal stem cells (MSCs) either obtained from tendons or from non-tendon sources, like bone marrow (BM-MSCs) or adipose tissue (ASCs), have been receiving increasing attention over the years toward enhancing tendon healing. Evidences from in vitro and in vivo studies suggest MSCs can contribute to accelerate and improve the quality of tendon healing. Nonetheless, the exact mechanisms underlying these repair events are yet to be fully elucidated. This review provides an overview of the main challenges in the field of cell-based regenerative therapies, discussing the role of MSCs in boosting tendon regeneration, particularly through their capacity to enhance the tenogenic properties of tendon resident cells.

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Gingival Mesenchymal Stem Cells Outperform Haploidentical Dental Pulp-derived Mesenchymal Stem Cells in Proliferation Rate, Migration Ability, and Angiogenic Potential

Cell Transplantation ◽

10.1177/0963689718759649 ◽

2018 ◽

Vol 27 (6) ◽

pp. 967-978 ◽

Cited By ~ 9

Author(s):

Ioannis Angelopoulos ◽

Claudia Brizuela ◽

Maroun Khoury

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Dental Pulp ◽

Migration Ability ◽

Differentiation Potential ◽

Angiogenic Potential ◽

Dental Tissues ◽

Vascular Growth Factor

High donor variation makes comparison studies between different dental sources dubious. Dental tissues offer a rare opportunity for comparing the biological characteristics of haploidentical mesenchymal stem cells (MSCs) isolated from the same donor. The objective was to identify the optimal dental source of MSCs through a biological and functional comparison of haploidentical MSCs from gingival (GMSCs) and dental pulp stem cells (DPSCs) focusing mainly on their angiogenic potential. The comparison study included (1) surface markers expression, (2) mesodermal differentiation capacity (chondrogenic, adipogenic, and osteogenic), (3) proliferation, (4) migration potential, (5) ability to form colony units, and (6) angiogenic potential in vitro and in vivo. Comparative analysis showed no difference in the immunophenotypic profile nor for the trilineage differentiation potential. Proliferation of GMSCs was higher than DPSCs at day 6 (2.6-fold higher, P < 0.05). GMSCs showed superior migratory capacity compared to DPSCs at 4, 8, and 12 h (2.1-, 1.5-, and 1.2-fold higher, respectively, P < 0.05). Furthermore, GMSCs formed a higher number of colony units for both cell concentrations (1.7- and 1.4-fold higher for 150 and 250 starting cells, respectively, P < 0.05). GMSCs showed an improved angiogenic capacity compared to DPSCs (total tube lengths 1.17-fold higher and 1.5-fold total loops, P < 0.05). This was correlated with an enhanced release of vascular growth factor under hypoxic conditions. Finally, in the plug transplantation assay evaluating the angiogenesis in vivo, the DPSC and GMSC hemoglobin content was 3.9- and 4-fold higher, respectively, when compared to the control (Matrigel alone). GMSCs were superior to their haploidentical DPSCs in proliferation, migration, and angiogenic potentials. This study positions GMSCs in the forefront of dental cell sources for applications in regenerative medicine.

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The Myokine Irisin Promotes Osteogenic Differentiation of Dental Bud-Derived MSCs

Biology ◽

10.3390/biology10040295 ◽

2021 ◽

Vol 10 (4) ◽

pp. 295

Author(s):

Francesca Posa ◽

Graziana Colaianni ◽

Michele Di Cosola ◽

Manuela Dicarlo ◽

Francesco Gaccione ◽

...

Keyword(s):

Stem Cells ◽

Osteogenic Differentiation ◽

Bone Tissue ◽

Osteoblastic Differentiation ◽

In Vivo Studies ◽

Matrix Deposition ◽

Dental Tissues ◽

Enhanced Expression

The myokine irisin, well known for its anabolic effect on bone tissue, has been demonstrated to positively act on osteoblastic differentiation processes in vitro. Mesenchymal stem cells (MSCs) have captured great attention in precision medicine and translational research for several decades due to their differentiation capacity, potent immunomodulatory properties, and their ability to be easily cultured and manipulated. Dental bud stem cells (DBSCs) are MSCs, isolated from dental tissues, that can effectively undergo osteoblastic differentiation. In this study, we analyzed, for the first time, the effects of irisin on DBSC osteogenic differentiation in vitro. Our results indicated that DBSCs were responsive to irisin, showed an enhanced expression of osteocalcin (OCN), a late marker of osteoblast differentiation, and displayed a greater mineral matrix deposition. These findings lead to deepening the mechanism of action of this promising molecule, as part of osteoblastogenesis process. Considering the in vivo studies of the effects of irisin on skeleton, irisin could improve bone tissue metabolism in MSC regenerative procedures.

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Can mesenchymal stem cells pretreated with platelet-rich plasma modulate tissue remodeling in a rat with burned skin?

Biochemistry and Cell Biology ◽

10.1139/bcb-2016-0224 ◽

2017 ◽

Vol 95 (5) ◽

pp. 537-548 ◽

Cited By ~ 9

Author(s):

Hanan Hosni Ahmed ◽

Laila Ahmed Rashed ◽

Sohair Mahfouz ◽

Rania Elsayed Hussein ◽

Marwa Alkaffas ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Transforming Growth Factor ◽

Burn Injury ◽

Platelet Rich Plasma ◽

In Vivo Studies ◽

Control Group ◽

Tnf Α

Our aim was to study the effect of platelet-rich plasma (PRP) on the proliferation of bone-marrow-derived mesenchymal stem cells (BM-MSCs) and to investigate their roles in the healing of experimental burn injury and the possible mechanism of action. Our work was divided into in-vitro and in-vivo studies. The in-vitro study included untreated MSCs and MSCs treated with PRP. Levels of TGF-β and cell proliferation were assessed. In the in-vivo study, 72 rats were distributed equally among 6 groups: control, burn, burn with MSCs, burn with PRP, burn with both MSCs and PRP, and burn with MSCs pretreated with PRP. On the 7th and 20th day after injury, the serum levels of transforming growth factor beta (TGF-β) and tumor necrosis factor alpha (TNF-α), as well as interleukin-10 (IL-10) levels in skin tissue were measured by ELISA; histopathology and gene expression of MMP-1, TIMP-2, Ang-1, Ang-2, and vimentin by real-time PCR were performed in all groups. In vitro: proliferation of MSCs and TGF-β increased in the PRP-treated group compared with the control group. In vivo: Ang-1, Ang-2, and vimentin were upregulated, whereas MMP-1 and TIMP-2 were downregulated. TGF-β and IL-10 were increased, whereas TNF-α was decreased in all treated groups with more significance in MSCs and PRP on day 20. Histopathology of burn skin was improved in all treated groups, particularly in MSCs pretreated with PRP 20 days post-burn.

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