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Recent Advances in Mesenchymal Stem Cell Immunomodulation and Regenerative Medicine...
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Recent Advances in Mesenchymal Stem Cell Immunomodulation and Regenerative Medicine 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (31 October 2020) | Viewed by 34614

Special Issue Editor

Dr. Andrea Del Fattore

E-Mail Website
Guest Editor
Bone Physiopathology Group, Multifactorial Disease and Complex Phenotype Research Area, Bambino Gesù Children’s Hospital, 00146 Rome, Italy
Interests: bone cell biology; bone diseases; bone regeneration; mesenchymal stem cells; osteoclasts; osteoblasts; osteocytes; extracellular vesicles
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The landscape of therapeutic applications based on mesenchymal stem cells is continuously increasing due to their well-established abilities to modulate immune responses and to promote the regeneration of injured tissues. MSC, like several other cell types, exert many of their effects via paracrine signalling, including the release of extracellular vesicles (exosomes and microvesicles).

Numerous studies have already demonstrated the beneficial uses of MSC in both preclinical research and clinical trials. Efficacy was reported in the treatment of several animal models of inflammatory and autoimmune diseases and, in clinical settings, for the management of disorders such as GVHD, systemic lupus erythematosus, multiple sclerosis, and inflammatory bowel disease.

The purpose of this Special Issue is to bring together research/review articles on the recent advances in mesenchymal stem cells in the treatment of immune disorders and to provide a concise overview of MSC-based cell therapy in tissue regeneration. Articles on the effects of MSC-released extracellular vesicles are particularly welcome.

Dr. Andrea Del Fattore
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • Mesenchymal stem cells
  • Immunomodulation
  • Regenerative medicine
  • Extracellular vesicles

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Published Papers (5 papers)

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Research

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17 pages, 2234 KiB  
Article
Secretome Analysis of Inductive Signals for BM-MSC Transdifferentiation into Salivary Gland Progenitors
by Mahmoud Mona, Firas Kobeissy, Yun-Jong Park, Rehae Miller, Wafaa Saleh, Jin Koh, Mi-Jeong Yoo, Sixue Chen and Seunghee Cha
Int. J. Mol. Sci. 2020, 21(23), 9055; https://doi.org/10.3390/ijms21239055 - 28 Nov 2020
Cited by 7 | Viewed by 3639
Abstract
Severe dry mouth in patients with Sjögren’s Syndrome, or radiation therapy for patients with head and neck cancer, significantly compromises their oral health and quality of life. The current clinical management of xerostomia is limited to palliative care as there are no clinically-proven [...] Read more.
Severe dry mouth in patients with Sjögren’s Syndrome, or radiation therapy for patients with head and neck cancer, significantly compromises their oral health and quality of life. The current clinical management of xerostomia is limited to palliative care as there are no clinically-proven treatments available. Previously, our studies demonstrated that mouse bone marrow-derived mesenchymal stem cells (mMSCs) can differentiate into salivary progenitors when co-cultured with primary salivary epithelial cells. Transcription factors that were upregulated in co-cultured mMSCs were identified concomitantly with morphological changes and the expression of acinar cell markers, such as α-amylase (AMY1), muscarinic-type-3-receptor(M3R), aquaporin-5(AQP5), and a ductal cell marker known as cytokeratin 19(CK19). In the present study, we further explored inductive molecules in the conditioned media that led to mMSC reprogramming by high-throughput liquid chromatography with tandem mass spectrometry and systems biology. Our approach identified ten differentially expressed proteins based on their putative roles in salivary gland embryogenesis and development. Additionally, systems biology analysis revealed six candidate proteins, namely insulin-like growth factor binding protein-7 (IGFBP7), cysteine-rich, angiogenetic inducer, 61(CYR61), agrin(AGRN), laminin, beta 2 (LAMB2), follistatin-like 1(FSTL1), and fibronectin 1(FN1), for their potential contribution to mMSC transdifferentiation during co-culture. To our knowledge, our study is the first in the field to identify soluble inductive molecules that drive mMSC into salivary progenitors, which crosses lineage boundaries. Full article
(This article belongs to the Special Issue Recent Advances in Mesenchymal Stem Cell Immunomodulation and Regenerative Medicine 2.0)
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21 pages, 1528 KiB  
Article
Comparative Proteomic Analysis Identifies EphA2 as a Specific Cell Surface Marker for Wharton’s Jelly-Derived Mesenchymal Stem Cells
by Ashraf Al Madhoun, Sulaiman K. Marafie, Dania Haddad, Motasem Melhem, Mohamed Abu-Farha, Hamad Ali, Sardar Sindhu, Maher Atari and Fahd Al-Mulla
Int. J. Mol. Sci. 2020, 21(17), 6437; https://doi.org/10.3390/ijms21176437 - 3 Sep 2020
Cited by 12 | Viewed by 3909
Abstract
Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) are a valuable tool in stem cell research due to their high proliferation rate, multi-lineage differentiation potential, and immunotolerance properties. However, fibroblast impurity during WJ-MSCs isolation is unavoidable because of morphological similarities and shared surface markers. Here, [...] Read more.
Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) are a valuable tool in stem cell research due to their high proliferation rate, multi-lineage differentiation potential, and immunotolerance properties. However, fibroblast impurity during WJ-MSCs isolation is unavoidable because of morphological similarities and shared surface markers. Here, a proteomic approach was employed to identify specific proteins differentially expressed by WJ-MSCs in comparison to those by neonatal foreskin and adult skin fibroblasts (NFFs and ASFs, respectively). Mass spectrometry analysis identified 454 proteins with a transmembrane domain. These proteins were then compared across the different cell-lines and categorized based on their cellular localizations, biological processes, and molecular functions. The expression patterns of a selected set of proteins were further confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blotting, and immunofluorescence assays. As anticipated, most of the studied proteins had common expression patterns. However, EphA2, SLC25A4, and SOD2 were predominantly expressed by WJ-MSCs, while CDH2 and Talin2 were specific to NFFs and ASFs, respectively. Here, EphA2 was established as a potential surface-specific marker to distinguish WJ-MSCs from fibroblasts and for prospective use to prepare pure primary cultures of WJ-MSCs. Additionally, CDH2 could be used for a negative-selection isolation/depletion method to remove neonatal fibroblasts contaminating preparations of WJ-MSCs. Full article
(This article belongs to the Special Issue Recent Advances in Mesenchymal Stem Cell Immunomodulation and Regenerative Medicine 2.0)
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Review

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22 pages, 740 KiB  
Review
Strategies for Bone Regeneration: From Graft to Tissue Engineering
by Giulia Battafarano, Michela Rossi, Viviana De Martino, Francesco Marampon, Luca Borro, Aurelio Secinaro and Andrea Del Fattore
Int. J. Mol. Sci. 2021, 22(3), 1128; https://doi.org/10.3390/ijms22031128 - 23 Jan 2021
Cited by 146 | Viewed by 14996
Abstract
Bone is a regenerative organ characterized by self-renewal ability. Indeed, it is a very dynamic tissue subjected to continuous remodeling in order to preserve its structure and function. However, in clinical practice, impaired bone healing can be observed in patients and medical intervention [...] Read more.
Bone is a regenerative organ characterized by self-renewal ability. Indeed, it is a very dynamic tissue subjected to continuous remodeling in order to preserve its structure and function. However, in clinical practice, impaired bone healing can be observed in patients and medical intervention is needed to regenerate the tissue via the use of natural bone grafts or synthetic bone grafts. The main elements required for tissue engineering include cells, growth factors and a scaffold material to support them. Three different materials (metals, ceramics, and polymers) can be used to create a scaffold suitable for bone regeneration. Several cell types have been investigated in combination with biomaterials. In this review, we describe the options available for bone regeneration, focusing on tissue engineering strategies based on the use of different biomaterials combined with cells and growth factors. Full article
(This article belongs to the Special Issue Recent Advances in Mesenchymal Stem Cell Immunomodulation and Regenerative Medicine 2.0)
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19 pages, 1559 KiB  
Review
JAK/STAT Activation: A General Mechanism for Bone Development, Homeostasis, and Regeneration
by Alexandra Damerau, Timo Gaber, Sarah Ohrndorf and Paula Hoff
Int. J. Mol. Sci. 2020, 21(23), 9004; https://doi.org/10.3390/ijms21239004 - 26 Nov 2020
Cited by 35 | Viewed by 5361
Abstract
The Janus kinase (JAK) signal transducer and activator of transcription (STAT) signaling pathway serves as an important downstream mediator for a variety of cytokines, hormones, and growth factors. Emerging evidence suggests JAK/STAT signaling pathway plays an important role in bone development, metabolism, and [...] Read more.
The Janus kinase (JAK) signal transducer and activator of transcription (STAT) signaling pathway serves as an important downstream mediator for a variety of cytokines, hormones, and growth factors. Emerging evidence suggests JAK/STAT signaling pathway plays an important role in bone development, metabolism, and healing. In this light, pro-inflammatory cytokines are now clearly implicated in these processes as they can perturb normal bone remodeling through their action on osteoclasts and osteoblasts at both intra- and extra-articular skeletal sites. Here, we summarize the role of JAK/STAT pathway on development, homeostasis, and regeneration based on skeletal phenotype of individual JAK and STAT gene knockout models and selective inhibition of components of the JAK/STAT signaling including influences of JAK inhibition in osteoclasts, osteoblasts, and osteocytes. Full article
(This article belongs to the Special Issue Recent Advances in Mesenchymal Stem Cell Immunomodulation and Regenerative Medicine 2.0)
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20 pages, 853 KiB  
Review
Differentiation Induction of Human Stem Cells for Corneal Epithelial Regeneration
by Kasem Theerakittayakorn, Hong Thi Nguyen, Jidapa Musika, Hataiwan Kunkanjanawan, Sumeth Imsoonthornruksa, Sirilak Somredngan, Mariena Ketudat-Cairns and Rangsun Parnpai
Int. J. Mol. Sci. 2020, 21(21), 7834; https://doi.org/10.3390/ijms21217834 - 22 Oct 2020
Cited by 17 | Viewed by 6072
Abstract
Deficiency of corneal epithelium causes vision impairment or blindness in severe cases. Transplantation of corneal epithelial cells is an effective treatment but the availability of the tissue source for those cells is inadequate. Stem cells can be induced to differentiate to corneal epithelial [...] Read more.
Deficiency of corneal epithelium causes vision impairment or blindness in severe cases. Transplantation of corneal epithelial cells is an effective treatment but the availability of the tissue source for those cells is inadequate. Stem cells can be induced to differentiate to corneal epithelial cells and used in the treatment. Multipotent stem cells (mesenchymal stem cells) and pluripotent stem cells (embryonic stem cells and induced pluripotent stem cells) are promising cells to address the problem. Various protocols have been developed to induce differentiation of the stem cells into corneal epithelial cells. The feasibility and efficacy of both human stem cells and animal stem cells have been investigated for corneal epithelium regeneration. However, some physiological aspects of animal stem cells are different from those of human stem cells, the protocols suited for animal stem cells might not be suitable for human stem cells. Therefore, in this review, only the investigations of corneal epithelial differentiation of human stem cells are taken into account. The available protocols for inducing the differentiation of human stem cells into corneal epithelial cells are gathered and compared. Also, the pathways involving in the differentiation are provided to elucidate the relevant mechanisms. Full article
(This article belongs to the Special Issue Recent Advances in Mesenchymal Stem Cell Immunomodulation and Regenerative Medicine 2.0)
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