Topical Collection "Mesenchymal Stem Cell Fate and Potential Therapy"

A topical collection in Biomolecules (ISSN 2218-273X). This collection belongs to the section "Molecular Biology".

Editor

Prof. Dr. Dafna Benayahu
E-Mail Website
Guest Editor
Tel Aviv University, Sackler Faculty of Medicine, Department of Cell and Developmental Biology, Ramal Aviv, Israel
Interests: mesenchymal stem cell fate; stem cells differentiation; cells niche; scaffolds biomaterial

Topical Collection Information

Dear Colleagues,

The study of stem cells within mesenchymal systems relates to cells derived from the bone and bone marrow, cartilage, muscle, and connective and adipose tissue. Stems are rare, and they allow the production of precursor cells in adult life that also maintains self-renewal and multilineage differentiation. A small population of multipotent cells have the capacity for their self-renewing and clonogenic capacity to generate progeny cells that are differentiated into various lineages.

Knowing how to identify the stem/progenitor cells to characterize and separate them can allow maintaining them into distinct subpopulations based on both phenotype and function. The stem cell differentiation relies on transcription factors and chromatin remodeling that play a role in the cells’ regulation. The regulation of cell fate decisions is profoundly influenced by systemic and local signals that provide the cells’ niche. Determining the cells’ fate is required both to maintain tissue homeostasis and function in tissue regeneration. The use of progenitor cells with scaffold biomaterial makes then an enormous power for medical devices in a variety of therapy applications.

Prof. Dr. Dafna Benayahu
Guest Editor

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Keywords

  • mesenchymal stem cell fate
  • stem/progenitors cells characterization
  • stem cell differentiation
  • cells niche
  • scaffold biomaterial

Published Papers (11 papers)

2021

Jump to: 2020

Article
Atelocollagen-Embedded Chondrocyte Precursors as a Treatment for Grade-4 Cartilage Defects of the Femoral Condyle: A Case Series with up to 9-Year Follow-Up
Biomolecules 2021, 11(7), 942; https://doi.org/10.3390/biom11070942 - 25 Jun 2021
Cited by 1 | Viewed by 1129
Abstract
We demonstrated the safety and efficacy of autologous chondrocyte precursor (CP) cell therapy in repairing Grade 4 cartilage defects of medial femoral condyles. The autologous bone marrow mesenchymal stem cells of each participant were isolated, amplified, and then differentiated into CPs in atelocollagen. [...] Read more.
We demonstrated the safety and efficacy of autologous chondrocyte precursor (CP) cell therapy in repairing Grade 4 cartilage defects of medial femoral condyles. The autologous bone marrow mesenchymal stem cells of each participant were isolated, amplified, and then differentiated into CPs in atelocollagen. Neotissues made of CPs were implanted into cartilage defects with an average cell density of 4.9 ± 2.1 × 106 cells/cm2 through arthrotomy. The knee function was evaluated with the International Knee Documentation Committee (IKDC) subjective knee form. Patients’ knee functions significantly improved by the 28th week (IKDC score = 68.3 ± 12.1), relative to the initial functionality before the CP therapy (IKDC score = 46.1 ± 16.4, p-value = 0.0014). Nine of these twelve patients maintained good knee functions for 9 years post-implantation (IKDC score = 69.8 ± 12.3) at levels higher than the pre-implantation values (p-value = 0.0018). Patients were evaluated with MRI and arthroscopy, and the defective sites exhibited a smooth surface without a gap between the implant and host tissue. This study demonstrates that autologous CPs successfully engraft into the host tissue and result in the re-formation of hyaline-like cartilage, thereby improving the impaired knee functions. Most importantly, no adverse event was reported during this long-term follow-up period. Full article
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Article
FITC-Dextran Release from Cell-Embedded Fibrin Hydrogels
Biomolecules 2021, 11(2), 337; https://doi.org/10.3390/biom11020337 - 23 Feb 2021
Cited by 2 | Viewed by 900
Abstract
Fibrin hydrogel is a central biological material in tissue engineering and drug delivery applications. As such, fibrin is typically combined with cells and biomolecules targeted to the regenerated tissue. Previous studies have analyzed the release of different molecules from fibrin hydrogels; however, the [...] Read more.
Fibrin hydrogel is a central biological material in tissue engineering and drug delivery applications. As such, fibrin is typically combined with cells and biomolecules targeted to the regenerated tissue. Previous studies have analyzed the release of different molecules from fibrin hydrogels; however, the effect of embedded cells on the release profile has yet to be quantitatively explored. This study focused on the release of Fluorescein isothiocyanate (FITC)-dextran (FD) 250 kDa from fibrin hydrogels, populated with different concentrations of fibroblast or endothelial cells, during a 48-h observation period. The addition of cells to fibrin gels decreased the overall release by a small percentage (by 7–15% for fibroblasts and 6–8% for endothelial cells) relative to acellular gels. The release profile was shown to be modulated by various cellular activities, including gel degradation and physical obstruction to diffusion. Cell-generated forces and matrix deformation (i.e., densification and fiber alignment) were not found to significantly influence the release profiles. This knowledge is expected to improve fibrin integration in tissue engineering and drug delivery applications by enabling predictions and ways to modulate the release profiles of various biomolecules. Full article
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Article
The Middle Part of the Plucked Hair Follicle Outer Root Sheath Is Identified as an Area Rich in Lineage-Specific Stem Cell Markers
Biomolecules 2021, 11(2), 154; https://doi.org/10.3390/biom11020154 - 25 Jan 2021
Cited by 5 | Viewed by 1231
Abstract
Hair follicle outer root sheath (ORS) is a putative source of stem cells with therapeutic capacity. ORS contains several multipotent stem cell populations, primarily in the distal compartment of the bulge region. However, the bulge is routinely obtained using invasive isolation methods, which [...] Read more.
Hair follicle outer root sheath (ORS) is a putative source of stem cells with therapeutic capacity. ORS contains several multipotent stem cell populations, primarily in the distal compartment of the bulge region. However, the bulge is routinely obtained using invasive isolation methods, which require human scalp tissue ex vivo. Non-invasive sampling has been standardized by means of the plucking procedure, enabling to reproducibly obtain the mid-ORS part. The mid-ORS shows potential for giving rise to multiple stem cell populations in vitro. To demonstrate the phenotypic features of distal, middle, and proximal ORS parts, gene and protein expression profiles were studied in physically separated portions. The mid-part of the ORS showed a comparable or higher NGFR, nestin/NES, CD34, CD73, CD44, CD133, CK5, PAX3, MITF, and PMEL expression on both protein and gene levels, when compared to the distal ORS part. Distinct subpopulations of cells exhibiting small and round morphology were characterized with flow cytometry as simultaneously expressing CD73/CD271, CD49f/CD105, nestin, and not CK10. Potentially, these distinct subpopulations can give rise to cultured neuroectodermal and mesenchymal stem cell populations in vitro. In conclusion, the mid part of the ORS holds the potential for yielding multiple stem cells, in particular mesenchymal stem cells. Full article
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Article
Kartogenin Enhances Chondrogenic Differentiation of MSCs in 3D Tri-Copolymer Scaffolds and the Self-Designed Bioreactor System
Biomolecules 2021, 11(1), 115; https://doi.org/10.3390/biom11010115 - 16 Jan 2021
Cited by 4 | Viewed by 1050
Abstract
Human cartilage has relatively slow metabolism compared to other normal tissues. Cartilage damage is of great clinical consequence since cartilage has limited intrinsic healing potential. Cartilage tissue engineering is a rapidly emerging field that holds great promise for tissue function repair and artificial/engineered [...] Read more.
Human cartilage has relatively slow metabolism compared to other normal tissues. Cartilage damage is of great clinical consequence since cartilage has limited intrinsic healing potential. Cartilage tissue engineering is a rapidly emerging field that holds great promise for tissue function repair and artificial/engineered tissue substitutes. However, current clinical therapies for cartilage repair are less than satisfactory and rarely recover full function or return the diseased tissue to its native healthy state. Kartogenin (KGN), a small molecule, can promote chondrocyte differentiation both in vitro and in vivo. The purpose of this research is to optimize the chondrogenic process in mesenchymal stem cell (MSC)-based chondrogenic constructs with KGN for potential use in cartilage tissue engineering. In this study, we demonstrate that KGN treatment can promote MSC condensation and cell cluster formation within a tri-copolymer scaffold. Expression of Acan, Sox9, and Col2a1 was significantly up-regulated in three-dimensional (3D) culture conditions. The lacuna-like structure showed active deposition of type II collagen and aggrecan deposition. We expect these results will open new avenues for the use of small molecules in chondrogenic differentiation protocols in combination with scaffolds, which may yield better strategies for cartilage tissue engineering. Full article
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Review
Efficacy and Safety of Mesenchymal Stem/Stromal Cell Therapy for Inflammatory Bowel Diseases: An Up-to-Date Systematic Review
Biomolecules 2021, 11(1), 82; https://doi.org/10.3390/biom11010082 - 11 Jan 2021
Cited by 12 | Viewed by 1206
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gut that can lead to severe gastrointestinal symptoms, malnutrition, and complications such as fistulas and cancer. Mesenchymal stem/stromal cells (MSCs) are being investigated as a novel therapy for IBD and have been [...] Read more.
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gut that can lead to severe gastrointestinal symptoms, malnutrition, and complications such as fistulas and cancer. Mesenchymal stem/stromal cells (MSCs) are being investigated as a novel therapy for IBD and have been demonstrated to be safe and effective for perianal fistulizing Crohn’s disease (PFCD). This systematic review aims to present the most recent studies on the safety and efficacy of MSC therapy in IBD. A detailed search strategy of clinical trials on MSCs and IBD was performed on PubMed, with 32 studies selected for inclusion in this review. The newest studies on local MSC injection for PFCD continue to support long-term efficacy while maintaining a favorable safety profile. The evidence for systemic MSC infusion in luminal IBD remains mixed due to marked methodological heterogeneity and unclear safety profiles. Although further studies are needed to better establish the role of this novel treatment modality, MSCs are proving to be a very exciting addition to the limited therapies available for IBD. Full article

2020

Jump to: 2021

Article
In Vitro Differentiation of Human Placenta-Derived Multipotent Cells into Schwann-Like Cells
Biomolecules 2020, 10(12), 1657; https://doi.org/10.3390/biom10121657 - 10 Dec 2020
Cited by 1 | Viewed by 642
Abstract
Human placenta-derived multipotent stem cells (PDMCs) resembling embryonic stem cells can differentiate into three germ layer cells, including ectodermal lineage cells, such as neurons, astrocytes, and oligodendrocytes. The favorable characteristics of noninvasive cell harvesting include fewer ethical, religious, and legal considerations as well [...] Read more.
Human placenta-derived multipotent stem cells (PDMCs) resembling embryonic stem cells can differentiate into three germ layer cells, including ectodermal lineage cells, such as neurons, astrocytes, and oligodendrocytes. The favorable characteristics of noninvasive cell harvesting include fewer ethical, religious, and legal considerations as well as accessible and limitless supply. Thus, PDMCs are attractive for cell-based therapy. The Schwann cell (SC) is the most common cell type used for tissue engineering such as nerve regeneration. However, the differentiation potential of human PDMCs into SCs has not been demonstrated until now. In this study, we evaluated the potential of PDMCs to differentiate into SC-like cells in a differentiation medium. After induction, PDMCs not only exhibited typical SC spindle-shaped morphology but also expressed SC markers, including S100, GFAP, p75, MBP, and Sox 10, as revealed by immunocytochemistry. Moreover, a reverse transcription-quantitative polymerase chain reaction analysis revealed the elevated gene expression of S100, GFAP, p75, MBP, Sox-10, and Krox-20 after SC induction. A neuroblastoma cell line, SH-SY5Y, was cultured in the conditioned medium (CM) collected from PDMC-differentiated SCs. The growth rate of the SH-SY5Y increased in the CM, indicating the function of PDMC-induced SCs. In conclusion, human PDMCs can be differentiated into SC-like cells and thus are an attractive alternative to SCs for cell-based therapy in the future. Full article
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Review
Clinical Translational Potential in Skin Wound Regeneration for Adipose-Derived, Blood-Derived, and Cellulose Materials: Cells, Exosomes, and Hydrogels
Biomolecules 2020, 10(10), 1373; https://doi.org/10.3390/biom10101373 - 27 Sep 2020
Cited by 7 | Viewed by 1991
Abstract
Acute and chronic skin wounds due to burns, pressure injuries, and trauma represent a substantial challenge to healthcare delivery with particular impacts on geriatric, paraplegic, and quadriplegic demographics worldwide. Nevertheless, the current standard of care relies extensively on preventive measures to mitigate pressure [...] Read more.
Acute and chronic skin wounds due to burns, pressure injuries, and trauma represent a substantial challenge to healthcare delivery with particular impacts on geriatric, paraplegic, and quadriplegic demographics worldwide. Nevertheless, the current standard of care relies extensively on preventive measures to mitigate pressure injury, surgical debridement, skin flap procedures, and negative pressure wound vacuum measures. This article highlights the potential of adipose-, blood-, and cellulose-derived products (cells, decellularized matrices and scaffolds, and exosome and secretome factors) as a means to address this unmet medical need. The current status of this research area is evaluated and discussed in the context of promising avenues for future discovery. Full article
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Review
Promising Opportunities for Treating Neurodegenerative Diseases with Mesenchymal Stem Cell-Derived Exosomes
Biomolecules 2020, 10(9), 1320; https://doi.org/10.3390/biom10091320 - 15 Sep 2020
Cited by 10 | Viewed by 1516
Abstract
Neurodegenerative disease refers to any pathological condition in which there is a progressive decline in neuronal function resulting from brain atrophy. Despite the immense efforts invested over recent decades in developing treatments for neurodegenerative diseases, effective therapy for these conditions is still an [...] Read more.
Neurodegenerative disease refers to any pathological condition in which there is a progressive decline in neuronal function resulting from brain atrophy. Despite the immense efforts invested over recent decades in developing treatments for neurodegenerative diseases, effective therapy for these conditions is still an unmet need. One of the promising options for promoting brain recovery and regeneration is mesenchymal stem cell (MSC) transplantation. The therapeutic effect of MSCs is thought to be mediated by their secretome, and specifically, by their exosomes. Research shows that MSC-derived exosomes retain some of the characteristics of their parent MSCs, such as immune system modulation, regulation of neurite outgrowth, promotion of angiogenesis, and the ability to repair damaged tissue. Here, we summarize the functional outcomes observed in animal models of neurodegenerative diseases following MSC-derived exosome treatment. We will examine the proposed mechanisms of action through which MSC-derived exosomes mediate their therapeutic effects and review advanced studies that attempt to enhance the improvement achieved using MSC-derived exosome treatment, with a view towards future clinical use. Full article
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Review
Mesenchymal Stem Cells as a Promising Cell Source for Integration in Novel In Vitro Models
Biomolecules 2020, 10(9), 1306; https://doi.org/10.3390/biom10091306 - 10 Sep 2020
Cited by 7 | Viewed by 1940
Abstract
The human-relevance of an in vitro model is dependent on two main factors—(i) an appropriate human cell source and (ii) a modeling platform that recapitulates human in vivo conditions. Recent years have brought substantial advancements in both these aspects. In particular, mesenchymal stem [...] Read more.
The human-relevance of an in vitro model is dependent on two main factors—(i) an appropriate human cell source and (ii) a modeling platform that recapitulates human in vivo conditions. Recent years have brought substantial advancements in both these aspects. In particular, mesenchymal stem cells (MSCs) have emerged as a promising cell source, as these cells can differentiate into multiple cell types, yet do not raise the ethical and practical concerns associated with other types of stem cells. In turn, advanced bioengineered in vitro models such as microfluidics, Organs-on-a-Chip, scaffolds, bioprinting and organoids are bringing researchers ever closer to mimicking complex in vivo environments, thereby overcoming some of the limitations of traditional 2D cell cultures. This review covers each of these advancements separately and discusses how the integration of MSCs into novel in vitro platforms may contribute enormously to clinical and fundamental research. Full article
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Article
Jaw Periosteal Cells Seeded in Beta-Tricalcium Phosphate Inhibit Dendritic Cell Maturation
Biomolecules 2020, 10(6), 887; https://doi.org/10.3390/biom10060887 - 10 Jun 2020
Cited by 2 | Viewed by 844
Abstract
Mesenchymal stem cells (MSCs) have gained attraction not only in the field of regenerative medicine but also in the field of autoimmune disease therapies or organ transplantation due to their immunoregulatory and/or immunosuppressive features. Dendritic cells (DCs) play a crucial role in initiating [...] Read more.
Mesenchymal stem cells (MSCs) have gained attraction not only in the field of regenerative medicine but also in the field of autoimmune disease therapies or organ transplantation due to their immunoregulatory and/or immunosuppressive features. Dendritic cells (DCs) play a crucial role in initiating and regulating immune reactions by promoting antigen-specific T cell activation. In this study, we investigated the effect of human jaw periosteal progenitor cells (JPCs) seeded in beta-tricalcium phosphate (β-TCP) scaffolds on monocyte-derived DC differentiation. Significantly lower numbers of differentiated DCs were observed in the presence of normal (Co) and osteogenically induced (Ob) JPCs-seeded β-TCP constructs. Gene expression analysis revealed significantly lower interleukin-12 subunit p35 (IL-12p35) and interleukin-12 receptor beta 2 (IL-12Rβ2) and pro-inflammatory cytokine interferon-gamma (IFN-γ) levels in DCs under Ob conditions, while interleukin-8 (IL-8) gene levels were significantly increased. Furthermore, in the presence of JPCs-seeded β-TCP constructs, interleukin-10 (IL-10) gene expression was significantly induced in DCs, particularly under Ob conditions. Analysis of DC protein levels shows that granulocyte-colony stimulating factor (G-CSF) was significantly upregulated in coculture groups. Our results indicate that undifferentiated and osteogenically induced JPCs-seeded β-TCP constructs have an overall inhibitory effect on monocyte-derived DC maturation. Full article
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Article
Mesenchymal Cell Growth and Differentiation on a New Biocomposite Material: A Promising Model for Regeneration Therapy
Biomolecules 2020, 10(3), 458; https://doi.org/10.3390/biom10030458 - 16 Mar 2020
Cited by 11 | Viewed by 996
Abstract
Mesenchymal stem cells serve as the body’s reservoir for healing and tissue regeneration. In cases of severe tissue trauma where there is also a need for tissue organization, a scaffold may be of use to support the cells in the damaged tissue. Such [...] Read more.
Mesenchymal stem cells serve as the body’s reservoir for healing and tissue regeneration. In cases of severe tissue trauma where there is also a need for tissue organization, a scaffold may be of use to support the cells in the damaged tissue. Such a scaffold should be composed of a material that can biomimic the mechanical and biological properties of the target tissues in order to support autologous cell-adhesion, their proliferation, and differentiation. In this study, we developed and assayed a new biocomposite made of unique collagen fibers and alginate hydrogel that was assessed for the ability to support mesenchymal cell-proliferation and differentiation. Analysis over 11 weeks in vitro demonstrated that the scaffold was biocompatible and supports the cells viability and differentiation to produce tissue-like structures or become adipocyte under differentiation medium. When the biocomposite was enriched with nano particles (NPs), mesenchymal cells grew well after uptake of fluorescein isothiocyanate (FITC) labeled NPs, maintained their viability, migrated through the biocomposite, reached, and adhered to the tissue culture dish. These promising findings revealed that the scaffold supports the growth and differentiation of mesenchymal cells that demonstrate their full physiological function with no sign of material toxicity. The cells’ functionality performance indicates and suggests that the scaffold is suitable to be developed as a new medical device that has the potential to support regeneration and the production of functional tissue. Full article
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