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Mesenchymal Stem/Stromal Cell Therapies: Innovations in Regenerative Medicine and Translational...
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Mesenchymal Stem/Stromal Cell Therapies: Innovations in Regenerative Medicine and Translational Applications

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

Deadline for manuscript submissions: 10 December 2026 | Viewed by 4254

Editors

Dr. Giandomenico Amico

E-Mail Website
Guest Editor
Ri.MED Foundation, Palermo, Italy
Interests: hematopoietic cells; human mesenchymal stromal/stem cells (MSCs); regenerative medicine; T, B and NK lymphocytes
Dr. Paolo Elia Cappella

E-Mail Website
Guest Editor
Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Lombardy, Italy
Interests: cell biology; immunology; low cytometry; oncology drug development

Special Issue Information

Dear Colleagues,

Human mesenchymal stem/stromal cells (hMSCs), as has been known for years, have extraordinary differentiation potential toward various lineages, namely adipogenic, chondrogenic, and osteogenic, as well as hepatic and pancreatic. Furthermore, their immunomodulatory properties make them a promising tool for application in the field of regenerative medicine. Based on extensive in vitro evidence, the immunological effects of MSCs on immune cells may depend on various mechanisms, such as cell-to-cell contact and paracrine signaling. MSCs also release exosomes capable of exerting various effects in a paracrine manner, influencing inflammatory processes.

This Special Issue of Cells will highlight the cell biology and immunology of MSCS through original research articles, reviews, and communications.

Dr. Giandomenico Amico
Dr. Paolo Elia Cappella
Guest Editors

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 communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

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-anonymized 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 (MSCs)
  • stromal cells
  • microvesicles
  • exosomes
  • extracellular vesicles (EVs)
  • immunomodulatory properties
  • bone marrow
  • adipose tissue
  • Wharton’s jelly
  • cord blood
  • placenta
  • amnion

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Published Papers (3 papers)

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Research

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37 pages, 19226 KB  
Article
Optimizing Photobiomodulation for Smooth Muscle Differentiation of Adipose-Derived Stem Cells Using Retinoic Acid and TGFβ in a Two-Dimensional Model
by Christevie Mbuyu, Heidi Abrahamse and Anine Crous
Cells 2026, 15(9), 789; https://doi.org/10.3390/cells15090789 - 27 Apr 2026
Viewed by 1258
Abstract
Smooth muscle (SM) dysfunction contributes to several pathological conditions, including atherosclerosis; current treatment strategies often fail to restore functional contractility. Adipose-derived stem cells (ADSCs) offer a promising cell source for regenerative medicine due to their accessibility and multipotency. Their differentiation into smooth muscle [...] Read more.
Smooth muscle (SM) dysfunction contributes to several pathological conditions, including atherosclerosis; current treatment strategies often fail to restore functional contractility. Adipose-derived stem cells (ADSCs) offer a promising cell source for regenerative medicine due to their accessibility and multipotency. Their differentiation into smooth muscle cells (SMC) is commonly driven by biochemical cues such as retinoic acid and transforming growth factor β; however, supporting this process with additional, non-invasive stimuli may enhance outcomes. Photobiomodulation (PBM) has emerged as a potential modulator of cellular metabolism, mitochondrial function and lineage commitment; however, its role in ADSCs to SMC differentiation remains insufficiently defined. ADSCs were irradiated with green (525 nm), near-infrared (825 nm) or dual wavelengths at 5 J/cm2 and 10 J/cm2 alongside the growth factors. Proliferation, cytotoxicity, mitochondrial membrane potential, collagen production, migration and smooth muscle marker expression were assessed. PBM induced a fluence-dependent biphasic response. 5 J/cm2 fluences enhanced proliferation, mitochondrial activity, collagen deposition and organized SMC marker expression, whereas 10 J/cm2 fluences lowered proliferation and membrane potential, reduced collagen and increased migration. PBM at 5 J/cm2, especially greenlight, most effectively promoted ADSCs’ progression towards a SMC-like phenotype, with features consistent with a more contractile-like state. Full article
(This article belongs to the Special Issue Mesenchymal Stem/Stromal Cell Therapies: Innovations in Regenerative Medicine and Translational Applications)
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Review

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21 pages, 1387 KB  
Review
Extracellular Vesicles in Cardiac Repair Approaches: Implications for In Vitro Heart Models and Potential ATMP Development
by Simona Di Stefani, Maura Cimino, Rosaria Tinnirello, Martina Maria Cocco, Cinzia Maria Chinnici, Giandomenico Amico, Valentina Di Felice, Filippo Macaluso, Bruno Douradinha, Paolo Di Nardo and Gioacchin Iannolo
Cells 2026, 15(10), 900; https://doi.org/10.3390/cells15100900 - 14 May 2026
Viewed by 831
Abstract
Cardiovascular diseases remain the leading cause of mortality in developed countries. Among these conditions, acute myocardial infarction (AMI) is associated with particularly high rates of cardiac morbidity and mortality. Cardiac development in mammals is primarily dependent on cardiomyocyte (CM) proliferation during embryonic and [...] Read more.
Cardiovascular diseases remain the leading cause of mortality in developed countries. Among these conditions, acute myocardial infarction (AMI) is associated with particularly high rates of cardiac morbidity and mortality. Cardiac development in mammals is primarily dependent on cardiomyocyte (CM) proliferation during embryonic and early postnatal stages. However, following birth, the proliferative capacity of CMs declines markedly, with only limited cellular renewal occurring during adult life in response to pathological injury. Consequently, the irreversible loss of functional cardiomyocytes and the subsequent formation of fibrotic scar tissue frequently lead to persistent cardiac dysfunction and progressive impairment of cardiac physiology. Cardiomyocyte self-renewal is a tightly regulated process involving multiple molecular pathways. Among factors implicated in this regulation, microRNAs (miRNAs) have emerged as key modulators coordinating both cardiac development and tissue repair mechanisms. In this context, extracellular vesicles (EVs) have attracted considerable interest as potential modulators of these regenerative processes. In particular, mesenchymal stromal cells (MSCs) represent a promising therapeutic platform due to their immunomodulatory and anti-fibrotic properties demonstrated across multiple in vitro and in vivo models. Furthermore, the therapeutic potential of MSC-derived EVs can be enhanced through bioengineering approaches aimed at improving targeted molecular delivery. In this review, we summarize recent advances in the development and application of EV-based therapeutic strategies, with particular emphasis on their potential use as advanced therapy medicinal products (ATMPs) for cardiovascular regeneration and repair. Full article
(This article belongs to the Special Issue Mesenchymal Stem/Stromal Cell Therapies: Innovations in Regenerative Medicine and Translational Applications)
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17 pages, 1303 KB  
Review
Chondrogenesis of Peripheral Blood-Derived Mesenchymal Stromal Cells
by Harish V. K. Ratna, Madhan Jeyaraman, Naveen Jeyaraman, Arulkumar Nallakumarasamy, Luise Schäfer, Filippo Migliorini and Sathish Muthu
Cells 2026, 15(5), 476; https://doi.org/10.3390/cells15050476 - 6 Mar 2026
Viewed by 1162
Abstract
Articular cartilage, a highly specialised and avascular tissue, exhibits limited regenerative potential following trauma or degenerative conditions such as osteoarthritis (OA). Conventional surgical interventions, including microfracture and autologous chondrocyte implantation (ACI), have shown limited long-term efficacy due to donor site morbidity and restricted [...] Read more.
Articular cartilage, a highly specialised and avascular tissue, exhibits limited regenerative potential following trauma or degenerative conditions such as osteoarthritis (OA). Conventional surgical interventions, including microfracture and autologous chondrocyte implantation (ACI), have shown limited long-term efficacy due to donor site morbidity and restricted cell proliferation. In this context, mesenchymal stromal cells (MSCs) have emerged as a promising alternative owing to their multipotency, self-renewal capacity, and low immunogenicity. While bone marrow (BM) remains the traditional source of MSCs, recent studies have reported that peripheral blood-derived mesenchymal stromal cells (PB-MSCs) may possess chondrogenic, osteogenic, and adipogenic potential comparable to that of BM-derived MSCs. PB-MSCs can be harvested through minimally invasive methods, thereby avoiding the complications associated with BM aspiration. Experimental evidence indicates that PB-MSCs exhibit strong cell viability, proliferative potential, and the ability to synthesise cartilage-specific extracellular matrix proteins, such as type II collagen and sulphated glycosaminoglycans, within three-dimensional scaffolds. Immunophenotypically, PB-MSCs express mesenchymal markers including CD29, CD44, CD90, and CD105 while lacking hematopoietic markers CD34 and CD45. Flow cytometry analyses reveal that CD105+ populations increase following cryopreservation, highlighting their clinical utility. In contrast to these experimentally defined PB-MSCs, the term peripheral blood stem cells (PBSCs) is used in clinical studies to describe heterogeneous, non-cultured peripheral blood-derived cell preparations, typically enriched in hematopoietic stem and progenitor cells following granulocyte colony-stimulating factor (G-CSF) mobilisation, without full mesenchymal characterisation. In vitro studies confirm successful tri-lineage differentiation, whereas in vivo investigations have demonstrated effective cartilage regeneration using PB-based clinical approaches, including postoperative intra-articular administration of hyaluronic acid (HA) combined with PBSCs, as well as implantation of PBSCs covered with a collagen membrane. Furthermore, advancements in biomaterial engineering, such as poly(ethylene glycol)–cysteine–arginine–glycine–aspartic acid (PEG-CRGD) hydrogels, have enhanced PB-MSC adhesion, proliferation, and chondrogenic differentiation while promoting immunomodulation through M2 macrophage polarisation. Despite these promising outcomes, the available evidence remains limited and heterogeneous, with substantial variability in cell definitions, experimental models, and clinical study designs, which currently constrains definitive conclusions regarding clinical efficacy. Future research should focus on optimising isolation protocols, understanding molecular pathways governing PB-MSC chondrogenesis, and standardising clinical applications. Overall, PB-MSCs represent a viable, less invasive, and translationally relevant cell source for cartilage regeneration and regenerative orthopaedic therapies Full article
(This article belongs to the Special Issue Mesenchymal Stem/Stromal Cell Therapies: Innovations in Regenerative Medicine and Translational Applications)
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