Submit to Cells Review for Cells Propose a Special Issue

Journal Browser

► Journal Browser

The Application of Mesenchymal Stem Cells in Tissue Regeneration

Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Tissues and Organs".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 9686

Share This Special Issue

Special Issue Editor

Dr. Xiaodong Chen

E-Mail Website
Guest Editor

School of Dentistry, The University of Texas at San Antonio, San Antonio, TX, USA
Interests: tissue regeneration; extracellular matrix; stem cells

Special Issue Information

Dear Colleagues,

Mesenchymal stem cells (MSCs) can self-renew and differentiate, serving as a “cell reservoir” for repairing damaged tissues caused by trauma or age-related diseases. In addition, MSCs also produce cytokines (trophic factors), acting as a “drug store” for attenuating inflammatory reactions and modulating the immune response for treating autoimmune diseases.

Since Friedenstein et al. discovered MSCs in bone marrow in 1974, these cells have been found in almost every tissue, including many that were considered as “non-regenerative”, such as the central nervous system, myocardium, skeletal muscle, and fat, and other atypical sources, such as umbilical cord blood, umbilical cord tissue (Wharton's jelly), amniotic fluid, dental pulp and periodontal ligament. In addition, embryonic stem cells (ESCs) and artificial ESCs (i.e. inducible pluripotent stem cells) have been shown to generate almost all types of cells in the body. Although MSCs from various sources share phenotypic similarities, each has its own unique characteristics that must be carefully investigated to demonstrate the advantages and disadvantages of their use for treating a particular disease.

In this Special Issue, the authors have prepared both reviews and reports of original research that focus on both the promises and challenges of these cells as potential therapeutic agents for treating a variety of diseases.

Dr. Xiaodong Chen
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

mesenchymal stem cells
stem cell niche
extracellular matrix
stem cell-based therapy
tissue regeneration
anti-aging

Published Papers (7 papers)

Download All Papers

Research

Jump to: Review

22 pages, 10069 KiB

Open AccessArticle

CREB1 Facilitates GABAergic Neural Differentiation of Human Mesenchymal Stem Cells through BRN2 for Pain Alleviation and Locomotion Recovery after Spinal Cord Injury

by Yanbing Kao, Hanming Zhu, Yu Yang, Wenyuan Shen, Wei Song, Renjie Zhang, Yanchun Liu, Haoyun Liu and Xiaohong Kong

Cells 2024, 13(1), 67; https://0-doi-org.brum.beds.ac.uk/10.3390/cells13010067 - 28 Dec 2023

Viewed by 1252

Abstract

The transplantation of GABAergic neuron cells has been reported to alleviate nerve pain and improve motor function after spinal cord injury (SCI). However, human mesenchymal stem cell (hMSC) differentiation into GABAergic neuron cells in a sufficient quantity remains to be accomplished. From a database screening, cAMP-responsive element-binding protein 1 (CREB1) was chosen as a potential modulator due to its critical role in the protein–protein interaction of genes related to GABAergic neural differentiation. Here, CREB1 was overexpressed in transfected hMSCs, where CREB1 could induce differentiation into GABAergic neuron cells with an upregulation of Map2 and GAD1 by 2- and 3.4-fold, respectively. Additionally, GABAergic neural differentiation was enhanced, while Notch signaling was inhibited, and BRN2 transcriptional activation played an important role in neuronal maturation. Moreover, transfected hMSCs injected into immunocompromised mice caused by CsA exhibited the neuronal markers Tuj1 and Map2 via the intraspinal route, suggesting an improvement in survival and neural differentiation. Significantly, improvement in both BMS scores (6.2 ± 1.30 vs. 4 ± 0) and thermal hyperalgesia latency (7.74 ± 2.36 s vs. 4.52 ± 0.39 s) was seen compared with the SCI naïve treatment at 4 weeks post-transplantation. Our study demonstrates that CREB1 is crucial in generating induced GABAergic neuron cells (iGNs) originating from hMSCs. Transplanting iGNs to injured spinal cord provides a promising strategy for alleviating neuropathic pain and locomotion recovery after SCI. Full article

(This article belongs to the Special Issue The Application of Mesenchymal Stem Cells in Tissue Regeneration)

► Show Figures

Figure 1

15 pages, 3567 KiB

Open AccessArticle

Treatment of Naturally Occurring Tendon Disease with Allogeneic Multipotent Mesenchymal Stromal Cells: A Randomized, Controlled, Triple-Blinded Pilot Study in Horses

by Janina Burk, Liza Wittenberg-Voges, Susanna Schubert, Carolin Horstmeier, Walter Brehm and Florian Geburek

Cells 2023, 12(21), 2513; https://0-doi-org.brum.beds.ac.uk/10.3390/cells12212513 - 24 Oct 2023

Cited by 3 | Viewed by 1201

Abstract

The treatment of tendinopathies with multipotent mesenchymal stromal cells (MSCs) is a promising option in equine and human medicine. However, conclusive clinical evidence is lacking. The purpose of this study was to gain insight into clinical treatment efficacy and to identify suitable outcome measures for larger clinical studies. Fifteen horses with early naturally occurring tendon disease were assigned to intralesional treatment with allogeneic adipose-derived MSCs suspended in serum or with serum alone through block randomization (dosage adapted to lesion size). Clinicians and horse owners remained blinded to the treatment during 12 months (seven horses per group) and 18 months (seven MSC-group and five control-group horses) of follow-up including clinical examinations and diagnostic imaging. Clinical inflammation, lameness, and ultrasonography scores improved more over time in the MSC group. The lameness score difference significantly improved in the MSC group compared with the control group after 6 months. In the MSC group, five out of the seven horses were free of re-injuries and back to training until 12 and 18 months. In the control group, three out of the seven horses were free of re-injuries until 12 months. These results suggest that MSCs are effective for the treatment of early-phase tendon disease and provide a basis for a larger controlled study. Full article

(This article belongs to the Special Issue The Application of Mesenchymal Stem Cells in Tissue Regeneration)

► Show Figures

Figure 1

12 pages, 2721 KiB

Open AccessArticle

Expression of Toll-like Receptors in Stem Cells of the Apical Papilla and Its Implication for Regenerative Endodontics

by Koyo Takimoto, Matthias Widbiller and Anibal Diogenes

Cells 2023, 12(20), 2502; https://0-doi-org.brum.beds.ac.uk/10.3390/cells12202502 - 21 Oct 2023

Viewed by 1127

Abstract

Regenerative therapies to replace cells and tissues damaged due to trauma and dental infections require temporal and spatial controlled recruitment and the differentiation of progenitor/stem cells. However, increasing evidence shows microbial antigens can interfere with this process. Toll-like receptors (TLRs) are crucial in recognizing pathogen-associated molecular patterns. Stem cells of the apical papilla (SCAP) are required for normal dental development and are intimately involved in the reparative and regenerative capacity of developing teeth. We hypothesized that TLRs are expressed in SCAP and that the activation of TLR2/TLR4 or TLR3 by different ligands results in differential cellular fate, impacting their differentiation into a mineralizing phenotype. We found that most TLRs are expressed as detected by PCR except TLR7 and TLR8; exposure to heat-killed E. coli results in upregulating TLR2 and TLR4 and reducing mineralization capacity. In addition, bacterial exposure resulted in the upregulation of 11 genes, of which 9 were chemokines whose proteins were also upregulated and released, promoting in vitro macrophage migration. On the other hand, TLR3 activation resulted in increased proliferation and a dramatic inhibition of osteogenic and odontoblastic differentiation, which was reversed by inhibition or the knockdown of TLR3 expression. The profound effects of TLR activation resulting in different cell fates that are ligand and receptor-specific warrants further evaluation and represents an important therapeutic target to make regenerative approaches more predictable following dental infections. Full article

(This article belongs to the Special Issue The Application of Mesenchymal Stem Cells in Tissue Regeneration)

► Show Figures

Figure 1

20 pages, 4601 KiB

Open AccessArticle

Pretreatment of Mesenchymal Stem Cells with Electrical Stimulation as a Strategy to Improve Bone Tissue Engineering Outcomes

by Santiago Bianconi, Karla M. C. Oliveira, Kari-Leticia Klein, Jakob Wolf, Alexander Schaible, Katrin Schröder, John Barker, Ingo Marzi, Liudmila Leppik and Dirk Henrich

Cells 2023, 12(17), 2151; https://0-doi-org.brum.beds.ac.uk/10.3390/cells12172151 - 26 Aug 2023

Cited by 2 | Viewed by 1419

Abstract

Electrical stimulation (EStim), whether used alone or in combination with bone tissue engineering (BTE) approaches, has been shown to promote bone healing. In our previous in vitro studies, mesenchymal stem cells (MSCs) were exposed to EStim and a sustained, long-lasting increase in osteogenic activity was observed. Based on these findings, we hypothesized that pretreating MSC with EStim, in 2D or 3D cultures, before using them to treat large bone defects would improve BTE treatments. Critical size femur defects were created in 120 Sprague–Dawley rats and treated with scaffold granules seeded with MSCs that were pre-exposed or not (control group) to EStim 1 h/day for 7 days in 2D (MSCs alone) or 3D culture (MSCs + scaffolds). Bone healing was assessed at 1, 4, and 8 weeks post-surgery. In all groups, the percentage of new bone increased, while fibrous tissue and CD68+ cell count decreased over time. However, these and other healing features, like mineral density, bending stiffness, the amount of new bone and cartilage, and the gene expression of osteogenic markers, did not significantly differ between groups. Based on these findings, it appears that the bone healing environment could counteract the long-term, pro-osteogenic effects of EStim seen in our in vitro studies. Thus, EStim seems to be more effective when administered directly and continuously at the defect site during bone healing, as indicated by our previous studies. Full article

(This article belongs to the Special Issue The Application of Mesenchymal Stem Cells in Tissue Regeneration)

► Show Figures

Graphical abstract

11 pages, 6110 KiB

Open AccessArticle

Autocrine Factors Produced by Mesenchymal Stem Cells in Response to Cell–Cell Contact Inhibition Have Anti-Tumor Properties

by Jerry P. Chen, Rong Li, Jean X. Jiang and Xiao-Dong Chen

Cells 2023, 12(17), 2150; https://0-doi-org.brum.beds.ac.uk/10.3390/cells12172150 - 26 Aug 2023

Cited by 1 | Viewed by 999

Abstract

Recently, mesenchymal stem cell (MSC) therapies have been questioned as MSCs are capable of both promoting and inhibiting tumorigenesis. Both MSCs and tumor cells replicate to increase their population size; however, MSCs, but not tumor cells, stop dividing when they reach confluence due to cell–cell contact inhibition and then differentiate. We hypothesized that contact inhibition results in the production of effector molecules by confluent MSCs and these effectors are capable of suppressing tumor cell growth. To test this hypothesis, we co-cultured breast cancer cells (MDA-MB-231) with either confluent or sub-confluent bone-marrow-derived MSCs (BM-MSCs); in addition, we treated various tumor cells with conditioned media (CM) obtained from either confluent or sub-confluent BM-MSCs. The results showed that the growth of tumor cells co-cultured with confluent BM-MSCs or treated with CM obtained from confluent BM-MSCs was inhibited, and this effect was significantly stronger than that seen with tumor cells co-cultured with sub-confluent BM-MSCs or CM obtained from sub-confluent BM-MSCs. Subcutaneous tumor formation was completely prevented by the inoculation of tumor cells mixed with CM. In the future, soluble anti-tumor effectors, produced by confluent MSCs, may be used as cell-free therapeutics; this approach provides a solution to current concerns associated with cell-based therapies. Full article

(This article belongs to the Special Issue The Application of Mesenchymal Stem Cells in Tissue Regeneration)

► Show Figures

Figure 1

31 pages, 12222 KiB

Open AccessArticle

Effect of Expansion Media on Functional Characteristics of Bone Marrow-Derived Mesenchymal Stromal Cells

by Viktoria Jakl, Tanja Popp, Julian Haupt, Matthias Port, Reinhild Roesler, Sebastian Wiese, Benedikt Friemert, Markus T. Rojewski and Hubert Schrezenmeier

Cells 2023, 12(16), 2105; https://0-doi-org.brum.beds.ac.uk/10.3390/cells12162105 - 19 Aug 2023

Cited by 2 | Viewed by 1426

Abstract

The therapeutic efficacy of mesenchymal stromal cells (MSCs) has been shown to rely on their immunomodulatory and regenerative properties. In order to obtain sufficient numbers of cells for clinical applications, MSCs have to be expanded ex vivo. Expansion media with xenogeneic-free (XF) growth-promoting supplements like human platelet lysate (PL) or serum- and xenogeneic-free (SF/XF) formulations have been established as safe and efficient, and both groups provide different beneficial qualities. In this study, MSCs were expanded in XF or SF/XF media as well as in mixtures thereof. MSCs cultured in these media were analyzed for phenotypic and functional properties. MSC expansion was optimal with SF/XF conditions when PL was present. Metabolic patterns, consumption of growth factors, and secretome of MSCs differed depending on the type and concentration of supplement. The lactate per glucose yield increased along with a higher proportion of PL. Many factors in the supernatant of cultured MSCs showed distinct patterns depending on the supplement (e.g., FGF-2, TGFβ, and insulin only in PL-expanded MSC, and leptin, sCD40L PDGF-AA only in SF/XF-expanded MSC). This also resulted in changes in cell characteristics like migratory potential. These findings support current approaches where growth media may be utilized for priming MSCs for specific therapeutic applications. Full article

(This article belongs to the Special Issue The Application of Mesenchymal Stem Cells in Tissue Regeneration)

► Show Figures

Graphical abstract

Review

Jump to: Research

17 pages, 998 KiB

Open AccessReview

Mesenchymal Stem/Stromal Cells for Therapeutic Angiogenesis

by Farina Mohamad Yusoff and Yukihito Higashi

Cells 2023, 12(17), 2162; https://0-doi-org.brum.beds.ac.uk/10.3390/cells12172162 - 28 Aug 2023

Viewed by 1442

Abstract

Mesenchymal stem/stromal cells (MSCs) are known to possess medicinal properties to facilitate vascular regeneration. Recent advances in the understanding of the utilities of MSCs in physiological/pathological tissue repair and technologies in isolation, expansion, and enhancement strategies have led to the use of MSCs for vascular disease-related treatments. Various conditions, including chronic arterial occlusive disease, diabetic ulcers, and chronic wounds, cause significant morbidity in patients. Therapeutic angiogenesis by cell therapy has led to the possibilities of treatment options in promoting angiogenesis, treating chronic wounds, and improving amputation-free survival. Current perspectives on the options for the use of MSCs for therapeutic angiogenesis in vascular research and in medicine, either as a monotherapy or in combination with conventional interventions, for treating patients with peripheral artery diseases are discussed in this review. Full article

(This article belongs to the Special Issue The Application of Mesenchymal Stem Cells in Tissue Regeneration)

► Show Figures