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18 pages, 5289 KiB

Open AccessArticle

Plasticity Comparison of Two Stem Cell Sources with Different Hox Gene Expression Profiles in Response to Cobalt Chloride Treatment during Chondrogenic Differentiation

by Sahar Khajeh, Vahid Razban, Yasaman Naeimzadeh, Elham Nadimi, Reza Asadi-Golshan, Zahra Heidari, Tahereh Talaei-Khozani, Farzaneh Dehghani, Zohreh Mostafavi-Pour and Masoud Shirali

Biology 2024, 13(8), 560; https://doi.org/10.3390/biology13080560 - 24 Jul 2024

Viewed by 996

Abstract

The limited self-repair capacity of articular cartilage is a challenge for healing injuries. While mesenchymal stem/stromal cells (MSCs) are a promising approach for tissue regeneration, the criteria for selecting a suitable cell source remain undefined. To propose a molecular criterion, dental pulp stem [...] Read more.

The limited self-repair capacity of articular cartilage is a challenge for healing injuries. While mesenchymal stem/stromal cells (MSCs) are a promising approach for tissue regeneration, the criteria for selecting a suitable cell source remain undefined. To propose a molecular criterion, dental pulp stem cells (DPSCs) with a Hox-negative expression pattern and bone marrow mesenchymal stromal cells (BMSCs), which actively express Hox genes, were differentiated towards chondrocytes in 3D pellets, employing a two-step protocol. The MSCs’ response to preconditioning by cobalt chloride (CoCl₂), a hypoxia-mimicking agent, was explored in an assessment of the chondrogenic differentiation’s efficiency using morphological, histochemical, immunohistochemical, and biochemical experiments. The preconditioned DPSC pellets exhibited significantly elevated levels of collagen II and glycosaminoglycans (GAGs) and reduced levels of the hypertrophic marker collagen X. No significant effect on GAGs production was observed in the preconditioned BMSC pellets, but collagen II and collagen X levels were elevated. While preconditioning did not modify the ALP specific activity in either cell type, it was notably lower in the DPSCs differentiated pellets compared to their BMSCs counterparts. These results could be interpreted as demonstrating the higher plasticity of DPSCs compared to BMSCs, suggesting the contribution of their unique molecular characteristics, including their negative Hox expression pattern, to promote a chondrogenic differentiation potential. Consequently, DPSCs could be considered compelling candidates for future cartilage cell therapy. Full article

(This article belongs to the Special Issue Mesenchymal Stem Cells: What We Have Learned and How to Manage Them)

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15 pages, 13450 KiB

Open AccessArticle

Immortalization of Mesenchymal Stem Cell Lines from Sheep Umbilical Cord Tissue

by Jinwei Yang, Yitong Dong, Lixinyi Hu, Weihai Wang, Yajun Li, Shujie Wang and Chunsheng Wang

Biology 2024, 13(7), 551; https://doi.org/10.3390/biology13070551 - 22 Jul 2024

Viewed by 1412

Abstract

Mesenchymal stem cells (MSCs) possess significant differentiation potential, making them highly promising in medicine and immunotherapy due to their regenerative capabilities and exosome secretion. However, challenges such as limited cell divisions and complex testing hinder large-scale MSC production. In this study, we successfully [...] Read more.

Mesenchymal stem cells (MSCs) possess significant differentiation potential, making them highly promising in medicine and immunotherapy due to their regenerative capabilities and exosome secretion. However, challenges such as limited cell divisions and complex testing hinder large-scale MSC production. In this study, we successfully established an immortalized MSC line by transfecting the human telomerase reverse transcriptase (TERT) gene into MSCs isolated from pregnant sheep umbilical cords. This approach effectively inhibits cell senescence and promotes cell proliferation, enabling the generation of umbilical cord mesenchymal stem cells (UCMSCs) on a larger scale. Our findings demonstrate that these transfected TERT-UCMSCs exhibit enhanced proliferative capacity and a reduced aging rate compared to regular UCMSCs while maintaining their stemness without tumorigenicity concerns. Consequently, they hold great potential for medical applications requiring large quantities of functional MSCs. Full article

(This article belongs to the Special Issue Mesenchymal Stem Cells: What We Have Learned and How to Manage Them)

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20 pages, 7537 KiB

Open AccessArticle

Myogenic Differentiation and Immunomodulatory Properties of Rat Adipose-Derived Mesenchymal Stem/Stromal Cells

by Sai Koung Ngeun, Miki Shimizu and Masahiro Kaneda

Biology 2024, 13(2), 72; https://doi.org/10.3390/biology13020072 - 25 Jan 2024

Cited by 3 | Viewed by 2080

Abstract

The myogenic differentiation potential of MSCs is a key factor in their potential use as a cell source for muscle tissue repair and regeneration. Additionally, evaluating the immunomodulatory properties of MSCs is important to highlight their potential for regulating inflammation and supporting tissue [...] Read more.

The myogenic differentiation potential of MSCs is a key factor in their potential use as a cell source for muscle tissue repair and regeneration. Additionally, evaluating the immunomodulatory properties of MSCs is important to highlight their potential for regulating inflammation and supporting tissue regeneration. Given the limited literature on muscle differentiation potential and immunomodulatory properties, this study aims to characterize rat ADP MSCs for treating muscle disease. We isolated MSCs from adipose tissues around the periscapular region of the rats. We used a monoculture method for the myogenic differentiation and modified the myogenic induction medium by supplementing it with the growth factors FGF, HGF, and IGF. In rat ADP MSCs, expression of the MSC-specific marker, CD90, was 87.7%, while CD44 was 42.8%. For genes involved in immunomodulation, IGF1 and TGFB1 were highly expressed, while IL6 was poorly expressed. In addition to their trilineage differentiation potential, ADP MSCs exhibited the capacity to differentiate into myogenic cell lines, as evidenced by changes in cell morphology, leading to elongated and aligned structures and the expression of the MyoD and MYOG antibodies. The study found that ADP MSCs show great clinical promise for muscle regeneration. Full article

(This article belongs to the Special Issue Mesenchymal Stem Cells: What We Have Learned and How to Manage Them)

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13 pages, 3603 KiB

Open AccessArticle

Preparation of Fibrinogen-Depleted Human Platelet Lysate to Support Heparin-Free Expansion of Umbilical Cord-Derived Mesenchymal Stem Cells

by Li Ting Kee, Yi Ting Lee, Chiew Yong Ng, Muhammad Najib Fathi Hassan, Min Hwei Ng, Zalina Mahmood, Suria Abdul Aziz and Jia Xian Law

Biology 2023, 12(8), 1085; https://doi.org/10.3390/biology12081085 - 3 Aug 2023

Cited by 1 | Viewed by 2504

Abstract

Human platelet lysate (hPL) has high levels of fibrinogen and coagulation factors, which can lead to gel and precipitate formation during storage and cell culture. Heparin derived from animals is commonly added to minimize these risks, but cannot completely eliminate them. Thus, this [...] Read more.

Human platelet lysate (hPL) has high levels of fibrinogen and coagulation factors, which can lead to gel and precipitate formation during storage and cell culture. Heparin derived from animals is commonly added to minimize these risks, but cannot completely eliminate them. Thus, this study proposes an alternative method to prepare fibrinogen-depleted hPL (Fd-hPL) that supports heparin-free expansion of mesenchymal stem cells (MSCs). hPL was added to heparin to prepare heparin-hPL (H-hPL), whilst Fd-hPL was prepared by adding calcium salt to hPL to remove the fibrin clot. The concentrations of calcium, fibrinogen, and growth factors in H-hPL and Fd-hPL were compared. The effects of H-hPL and Fd-hPL on umbilical cord-derived MSCs (UC-MSCs) were assessed. The results showed that Fd-hPL possessed a significantly higher calcium concentration and a lower fibrinogen level than H-hPL. The concentrations of BDNF, TGF-β1, and PDGF-BB showed no significant difference between H-hPL and Fd-hPL, but Fd-hPL had a lower VEGF concentration. Fd-hPL retained the characteristics of UC-MSCs, as it did not affect the cell viability, proliferation, multilineage differentiation potential, or surface marker expression. In conclusion, Fd-hPL effectively supported the in vitro expansion of MSCs without compromising their characteristics, positioning it as a potential substitute for FBS in MSC culture. Full article

(This article belongs to the Special Issue Mesenchymal Stem Cells: What We Have Learned and How to Manage Them)

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18 pages, 3576 KiB

Open AccessArticle

3D Culture and Interferon-γ Priming Modulates Characteristics of Mesenchymal Stromal/Stem Cells by Modifying the Expression of Both Intracellular and Exosomal microRNAs

by Matteo Bulati, Alessia Gallo, Giovanni Zito, Rosalia Busà, Gioacchin Iannolo, Nicola Cuscino, Salvatore Castelbuono, Claudia Carcione, Claudio Centi, Gennaro Martucci, Alessandro Bertani, Maria Pia Baiamonte, Cinzia Maria Chinnici, Pier Giulio Conaldi and Vitale Miceli

Biology 2023, 12(8), 1063; https://doi.org/10.3390/biology12081063 - 28 Jul 2023

Cited by 6 | Viewed by 2024

Abstract

Mesenchymal stromal/stem cells (MSCs) have emerged as a therapeutic tool in regenerative medicine. Recent studies have shown that exosome (EXO)-derived microRNAs (miRNAs) play a crucial role in mediating MSC functions. Additionally, intracellular miRNAs have been found to regulate MSC therapeutic capacities. However, the [...] Read more.

Mesenchymal stromal/stem cells (MSCs) have emerged as a therapeutic tool in regenerative medicine. Recent studies have shown that exosome (EXO)-derived microRNAs (miRNAs) play a crucial role in mediating MSC functions. Additionally, intracellular miRNAs have been found to regulate MSC therapeutic capacities. However, the molecular mechanisms underlying miRNA-mediated MSC effects are not fully understood. We used 3D culture and IFN-γ to prime/enhance the MSC therapeutic effects in terms of functional miRNAs. After priming, our analysis revealed stable variations in intracellular miRNA among the MSC biological replicates. Conversely, a significant variability of miRNA was observed among EXOs released from biological replicates of the priming treatment. For each priming, we observed distinct miRNA expression profiles between the MSCs and their EXOs. Moreover, in both types of priming, gene ontology (GO) analysis of deregulated miRNAs highlighted their involvement in tissue repair/regeneration pathways. In particular, the 3D culture enhanced angiogenic properties in both MSCs and EXOs, while IFN-γ treatment enriched miRNAs associated with immunomodulatory pathways. These findings suggest that 3D culture and IFN-γ treatment are promising strategies for enhancing the therapeutic potential of MSCs by modulating miRNA expression. Additionally, the identified miRNAs may contribute to understanding the molecular mechanisms underlying the miRNA-mediated therapeutic effects of MSCs. Full article

(This article belongs to the Special Issue Mesenchymal Stem Cells: What We Have Learned and How to Manage Them)

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17 pages, 4447 KiB

Open AccessArticle

Contrariety of Human Bone Marrow Mesenchymal Stromal Cell Functionality in Modulating Circulatory Myeloid and Plasmacytoid Dendritic Cell Subsets

by Crystal C. Uwazie, Tyler U. Faircloth, Rhett N. Parr, Yenamala U. Reddy, Peiman Hematti, Devi Rajan and Raghavan Chinnadurai

Biology 2023, 12(5), 725; https://doi.org/10.3390/biology12050725 - 16 May 2023

Cited by 2 | Viewed by 1717

Abstract

Mesenchymal Stromal Cells (MSCs) derived from bone marrow are widely tested in clinical trials as a cellular therapy for potential inflammatory disorders. The mechanism of action of MSCs in mediating immune modulation is of wide interest. In the present study, we investigated the [...] Read more.

Mesenchymal Stromal Cells (MSCs) derived from bone marrow are widely tested in clinical trials as a cellular therapy for potential inflammatory disorders. The mechanism of action of MSCs in mediating immune modulation is of wide interest. In the present study, we investigated the effect of human bone-marrow-derived MSCs in modulating the circulating peripheral blood dendritic cell responses through flow cytometry and multiplex secretome technology upon their coculture ex vivo. Our results demonstrated that MSCs do not significantly modulate the responses of plasmacytoid dendritic cells. However, MSCs dose-dependently promote the maturation of myeloid dendritic cells. Mechanistic analysis showed that dendritic cell licensing cues (Lipopolysaccharide and Interferon-gamma) stimulate MSCs to secret an array of dendritic cell maturation-associated secretory factors. We also identified that MSC-mediated upregulation of myeloid dendritic cell maturation is associated with the unique predictive secretome signature. Overall, the present study demonstrated the dichotomy of MSC functionality in modulating myeloid and plasmacytoid dendritic cells. This study provides clues that clinical trials need to investigate if circulating dendritic cell subsets in MSC therapy can serve as potency biomarkers. Full article

(This article belongs to the Special Issue Mesenchymal Stem Cells: What We Have Learned and How to Manage Them)

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11 pages, 2401 KiB

Open AccessArticle

The Impact of Corticosteroid Administration at Different Time Points on Mucosal Wound Healing in Rats: An Experimental Pilot In Vivo Study

by Evgeny Weinberg, Nirit Tagger-Green, Michal Lusthaus, Marilena Vered, Eitan Mijiritsky, Liat Chaushu and Roni Kolerman

Biology 2022, 11(9), 1309; https://doi.org/10.3390/biology11091309 - 2 Sep 2022

Cited by 1 | Viewed by 2633

Abstract

Background: Conflicting results were found regarding the effect of corticosteroid (CS) administration upon wound healing. The objective of this pilot study was to evaluate the impact of CS administration at different time points on palatal wound healing in rats. Methods: A 4.2 mm [...] Read more.

Background: Conflicting results were found regarding the effect of corticosteroid (CS) administration upon wound healing. The objective of this pilot study was to evaluate the impact of CS administration at different time points on palatal wound healing in rats. Methods: A 4.2 mm diameter punch created a secondary healing excisional palatal defect in thirty-six (36) Wistar-derived, two-month-old male rats weighing 250–270 g. We evaluated the effect of CS by comparing wound healing between three equal groups: 12 rats who were not exposed to CS and two additional groups in which 1 mg/kg dexamethasone (1 mg/kg) was administered daily, early (1–4 days) and late (5–9 days) after injury. The dynamics of the healing process were evaluated weekly in 4 sacrificed rats from each group for three weeks. The wound area was assessed both macroscopically and microscopically; the inflammation score was assessed microscopically. Results: The initial wound area in all the rats was 13.85 mm². At the end of the study, it decreased to 4.11 ± 0.88 mm², 7.32 ± 2.11 mm², and 8.87 ± 3.01 mm² in control, early, and late CS administration groups, respectively (p = 0.075). Inflammation scores showed a tendency to decrease in the third week in all groups, with no statistical differences. Conclusions: Our findings do not support the positive impact of CS administration on palatal wound healing. While microscopically, we found no difference between the CS and control groups, CS exposure was associated with a macroscopically larger final wound area, reflecting a possible harmful effect of CS. Full article

(This article belongs to the Special Issue Mesenchymal Stem Cells: What We Have Learned and How to Manage Them)

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Review

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14 pages, 913 KiB

Open AccessReview

The Migration and the Fate of Dental Pulp Stem Cells

by Nadia Lampiasi

Biology 2023, 12(5), 742; https://doi.org/10.3390/biology12050742 - 19 May 2023

Cited by 7 | Viewed by 2626

Abstract

Human dental pulp stem cells (hDPSCs) are adult mesenchymal stem cells (MSCs) obtained from dental pulp and derived from the neural crest. They can differentiate into odontoblasts, osteoblasts, chondrocytes, adipocytes and nerve cells, and they play a role in tissue repair and regeneration. [...] Read more.

Human dental pulp stem cells (hDPSCs) are adult mesenchymal stem cells (MSCs) obtained from dental pulp and derived from the neural crest. They can differentiate into odontoblasts, osteoblasts, chondrocytes, adipocytes and nerve cells, and they play a role in tissue repair and regeneration. In fact, DPSCs, depending on the microenvironmental signals, can differentiate into odontoblasts and regenerate dentin or, when transplanted, replace/repair damaged neurons. Cell homing depends on recruitment and migration, and it is more effective and safer than cell transplantation. However, the main limitations of cell homing are the poor cell migration of MSCs and the limited information we have on the regulatory mechanism of the direct differentiation of MSCs. Different isolation methods used to recover DPSCs can yield different cell types. To date, most studies on DPSCs use the enzymatic isolation method, which prevents direct observation of cell migration. Instead, the explant method allows for the observation of single cells that can migrate at two different times and, therefore, could have different fates, for example, differentiation and self-renewal. DPSCs use mesenchymal and amoeboid migration modes with the formation of lamellipodia, filopodia and blebs, depending on the biochemical and biophysical signals of the microenvironment. Here, we present current knowledge on the possible intriguing role of cell migration, with particular attention to microenvironmental cues and mechanosensing properties, in the fate of DPSCs. Full article

(This article belongs to the Special Issue Mesenchymal Stem Cells: What We Have Learned and How to Manage Them)

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29 pages, 2277 KiB

Open AccessReview

Cell-Free Therapies: The Use of Cell Extracts to Mitigate Irradiation-Injured Salivary Glands

by Xinyun Su, Akshaya Upadhyay, Simon D. Tran and Zhengmei Lin

Biology 2023, 12(2), 305; https://doi.org/10.3390/biology12020305 - 14 Feb 2023

Cited by 6 | Viewed by 3079

Abstract

Radiotherapy is a standard treatment for head and neck cancer patients worldwide. However, millions of patients who received radiotherapy consequently suffer from xerostomia because of irreversible damage to salivary glands (SGs) caused by irradiation (IR). Current treatments for IR-induced SG hypofunction only provide [...] Read more.

Radiotherapy is a standard treatment for head and neck cancer patients worldwide. However, millions of patients who received radiotherapy consequently suffer from xerostomia because of irreversible damage to salivary glands (SGs) caused by irradiation (IR). Current treatments for IR-induced SG hypofunction only provide temporary symptom alleviation but do not repair the damaged SG, thus resulting in limited treatment efficacy. Therefore, there has recently been a growing interest in regenerative treatments, such as cell-free therapies. This review aims to summarize cell-free therapies for IR-induced SG, with a particular emphasis on utilizing diverse cell extract (CE) administrations. Cell extract is a group of heterogeneous mixtures containing multifunctional inter-cellular molecules. This review discusses the current knowledge of CE’s components and efficacy. We propose optimal approaches to improve cell extract treatment from multiple perspectives (e.g., delivery routes, preparation methods, and other details regarding CE administration). In addition, the advantages and limitations of CE treatment are systematically discussed by comparing it to other cell-free (such as conditioned media and exosomes) and cell-based therapies. Although a comprehensive identification of the bioactive factors within CEs and their mechanisms of action have yet to be fully understood, we propose cell extract therapy as an effective, practical, user-friendly, and safe option to conventional therapies in IR-induced SG. Full article

(This article belongs to the Special Issue Mesenchymal Stem Cells: What We Have Learned and How to Manage Them)

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27 pages, 3614 KiB

Open AccessReview

Aging and Mesenchymal Stem Cells: Basic Concepts, Challenges and Strategies

by Maria Fraile, Noemi Eiro, Luis A. Costa, Arancha Martín and Francisco J. Vizoso

Biology 2022, 11(11), 1678; https://doi.org/10.3390/biology11111678 - 18 Nov 2022

Cited by 22 | Viewed by 6471

Abstract

Aging and frailty are complex processes implicating multifactorial mechanisms, such as replicative senescence, oxidative stress, mitochondrial dysfunction, or autophagy disorder. All of these mechanisms drive dramatic changes in the tissue environment, such as senescence-associated secretory phenotype factors and inflamm-aging. Thus, there is a [...] Read more.

Aging and frailty are complex processes implicating multifactorial mechanisms, such as replicative senescence, oxidative stress, mitochondrial dysfunction, or autophagy disorder. All of these mechanisms drive dramatic changes in the tissue environment, such as senescence-associated secretory phenotype factors and inflamm-aging. Thus, there is a demand for new therapeutic strategies against the devastating effects of the aging and associated diseases. Mesenchymal stem cells (MSC) participate in a “galaxy” of tissue signals (proliferative, anti-inflammatory, and antioxidative stress, and proangiogenic, antitumor, antifibrotic, and antimicrobial effects) contributing to tissue homeostasis. However, MSC are also not immune to aging. Three strategies based on MSC have been proposed: remove, rejuvenate, or replace the senescent MSC. These strategies include the use of senolytic drugs, antioxidant agents and genetic engineering, or transplantation of younger MSC. Nevertheless, these strategies may have the drawback of the adverse effects of prolonged use of the different drugs used or, where appropriate, those of cell therapy. In this review, we propose the new strategy of “Exogenous Restitution of Intercellular Signalling of Stem Cells” (ERISSC). This concept is based on the potential use of secretome from MSC, which are composed of molecules such as growth factors, cytokines, and extracellular vesicles and have the same biological effects as their parent cells. To face this cell-free regenerative therapy challenge, we have to clarify key strategy aspects, such as establishing tools that allow us a more precise diagnosis of aging frailty in order to identify the therapeutic requirements adapted to each case, identify the ideal type of MSC in the context of the functional heterogeneity of these cellular populations, to optimize the mass production and standardization of the primary materials (cells) and their secretome-derived products, to establish the appropriate methods to validate the anti-aging effects and to determine the most appropriate route of administration for each case. Full article

(This article belongs to the Special Issue Mesenchymal Stem Cells: What We Have Learned and How to Manage Them)

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27 pages, 698 KiB

Open AccessReview

Autologous Platelet Concentrates (APCs) for Hard Tissue Regeneration in Oral Implantology, Sinus Floor Elevation, Peri-Implantitis, Socket Preservation, and Medication-Related Osteonecrosis of the Jaw (MRONJ): A Literature Review

by Eitan Mijiritsky, Haya Drora Assaf, Roni Kolerman, Luca Mangani, Vasilena Ivanova and Stefan Zlatev

Biology 2022, 11(9), 1254; https://doi.org/10.3390/biology11091254 - 23 Aug 2022

Cited by 12 | Viewed by 3218

Abstract

Over recent years, the usage of autologous platelet concentrates (APCs) has risen in hard tissue regeneration and oral implantology. The purpose of the present review is to offer an overview of the use of three APC techniques in dentistry: platelet-rich plasma (PRP), platelet-rich [...] Read more.

Over recent years, the usage of autologous platelet concentrates (APCs) has risen in hard tissue regeneration and oral implantology. The purpose of the present review is to offer an overview of the use of three APC techniques in dentistry: platelet-rich plasma (PRP), platelet-rich fibrin (PRF), and concentrated growth factor (CGF). A narrative summary of articles published between January 2011 and April 2022 is provided. The PubMed, Cochrane Library, Scopus, and Embase databases were used to conduct the search. The following keywords were used in the preliminary: “VEGF”, “TGF-b1”, “PRP”, “PRF”, “CGF”, AND “sinus augmentation” OR “implants” OR “peri-implantitis” OR “socket preservation” OR “MRONJ”. A total of 82 articles was finally included. The review then takes into account the application of the three techniques in different areas of treatment—including oral implantology, sinus floor elevation, peri-implantitis, socket preservation, and medication-related osteonecrosis of the jaw (MRONJ)—as well as their advantages and disadvantages. Full article

(This article belongs to the Special Issue Mesenchymal Stem Cells: What We Have Learned and How to Manage Them)

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