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Cells
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Stem Cells in Action: Unlocking the Potential of Next-Generation Therapies
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Stem Cells in Action: Unlocking the Potential of Next-Generation Therapies

A Special Issue of Cells (ISSN 2073-4409) belonging to the section "Stem Cells".

Deadline for manuscript submissions: closed (25 April 2026) | Viewed by 6329

Editor

Dr. George G. Koliakos

E-Mail Website
Guest Editor
Laboratory of Biological Chemistry, Medical School, Faculty of Health Sciences, Aristotle University, 54124 Thessaloniki, Greece
Interests: stem cells; molecular biology of the cell; gerobiology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Stem cells, with their unique capacity for self-renewal, differentiation, and paracrine signaling, serve as foundational elements in modern biomedical science. This Special Issue will showcase groundbreaking research and expert perspectives on the multifaceted functions of stem cells in regenerative medicine, disease modeling, and therapeutic innovation. We particularly welcome contributions that elucidate the molecular and cellular mechanisms governing stem cell behavior—ranging from lineage commitment and niche interaction to immunomodulatory and antimicrobial functions—as well as studies investigating the therapeutic utility of stem cell-derived secretomes and extracellular vesicles, as well as the utility of organoid systems in personalized and general drug evaluation and tissue repair. Additionally, applications spanning tissue repair, scaffold-based engineering, and translational strategies—including cGMP-compliant protocols and clinical‑grade production—are of significant interest. By fostering dialogue across basic biology, bioengineering, and clinical translation, this Special Issue will spotlight innovations that harness stem cells’ intrinsic capabilities in tissue regeneration, disease intervention, and personalized medicine. We invite the original submission of research, reviews, methods, and perspectives that will advance our understanding of stem cell functions and pave the way for next-generation biomedical applications.

Dr. George G. Koliakos
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 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

  • stem cell biology
  • differentiation and niche interaction
  • secretome/extracellular vesicles
  • organoids and disease modeling
  • regenerative medicine and tissue repair
  • immunomodulation and antimicrobial function
  • cell-based therapies and cGMP translation
  • scaffold and biomaterial integration

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Published Papers (4 papers)

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Research

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20 pages, 19722 KB  
Article
Preclinical Evaluation of Human Donor-Derived Micronized Bone Marrow Stroma/Parenchyma Versus Bone Marrow Aspirate Concentrate in a Rat Model of Post-Traumatic Knee Osteoarthritis
by Haruki Nishimura, Zuokui Xiao, Jacob Singer, Xueqin Gao, William Sealy Hambright, Ryan Dregalla, Christopher T. Donner, Lucanus S. Koldewyn, Edward Jeffrey Donner and Johnny Huard
Cells 2026, 15(14), 1249; https://doi.org/10.3390/cells15141249 - 10 Jul 2026
Viewed by 581
Abstract
Bone marrow aspirate concentrate (BMAC) is widely used as a source of mesenchymal stromal/stem cells (MSCs) for musculoskeletal regeneration; however, BMAC lacks essential bone marrow extracellular matrix (ECM) components, a critical component of the stem cell niche that regulates MSC survival, paracrine signaling, [...] Read more.
Bone marrow aspirate concentrate (BMAC) is widely used as a source of mesenchymal stromal/stem cells (MSCs) for musculoskeletal regeneration; however, BMAC lacks essential bone marrow extracellular matrix (ECM) components, a critical component of the stem cell niche that regulates MSC survival, paracrine signaling, and regenerative capacity. We previously demonstrated that an ECM-retaining micronized bone marrow product (BMAX™) preserves pro-regenerative MSC phenotypes in vitro. Human bone marrow from a single donor was processed into conventional BMAC or BMAX™. Post-traumatic osteoarthritis was induced in immunodeficient rats using destabilization of the medial meniscus (DMM). Four weeks after surgery, animals were randomly assigned to receive intra-articular injections of BMAX™, BMAC, or phosphate-buffered saline (n = 10–12 in each group). Pain-related behavior (n = 5–6/group), histological assessment (n = 3–6/group), and micro-computed tomography (n = 4–6/group) were evaluated for up to 8 weeks after treatment. At 4 weeks after treatment, BMAC significantly increased the paw withdrawal threshold compared with PBS (p = 0.0068), whereas BMAX™ significantly reduced knee joint swelling compared with both PBS (p = 0.0235) and BMAC (p = 0.0039), and BMAX™ significantly improved knee bend scores compared with PBS (p = 0.0011). Neither treatment significantly improved OARSI histological scores at this time point. At 8 weeks after treatment, BMAX™ significantly increased the paw withdrawal threshold compared with PBS (p = 0.0305), whereas BMAC showed a non-significant trend (p = 0.0517); both treatments significantly reduced knee bend scores compared with PBS (p = 0.0027 and p = 0.0255), and BMAX™ demonstrated significantly lower knee bend scores than BMAC (p = 0.0090). BMAX™ significantly reduced knee swelling compared with PBS (p = 0.0196). Histologically, BMAX™ significantly improved OARSI scores in both the femoral condyle and tibial plateau compared with PBS (p = 0.0020 and p = 0.0003, respectively), whereas BMAC significantly improved only tibial plateau OARSI scores (p = 0.0014). Furthermore, BMAX™ demonstrated significantly lower femoral condyle OARSI scores than BMAC (p = 0.0243). Micro-computed tomography revealed that both BMAX™ and BMAC significantly reduced medial subchondral trabecular separation compared with PBS (p = 0.0340 and p = 0.0426, respectively), whereas no significant differences were observed between the two treatment groups for other bone structural parameters. In conclusion, preservation of the native bone marrow ECM was associated with improved functional outcomes and greater cartilage regeneration compared with conventional BMAC in this preclinical rat model of post-traumatic osteoarthritis. These findings support the concept that maintaining the native stem cell niche may enhance the therapeutic potential of bone marrow-derived cell therapies for osteoarthritis. Full article
(This article belongs to the Special Issue Stem Cells in Action: Unlocking the Potential of Next-Generation Therapies)
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Review

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19 pages, 1084 KB  
Review
Influence of Donor Obesity on Adipose-Derived Stem Cell Function and Therapeutic Efficacy
by Marva Khalid, Marvin L. Frommer, Jeries Abu-Hanna, Benjamin J. Langridge, Clara Calero Pages, Laura Awad and Peter E. M. Butler
Cells 2026, 15(10), 946; https://doi.org/10.3390/cells15100946 - 21 May 2026
Viewed by 796
Abstract
Adipose-derived stem cells (ADSCs) are widely used in regenerative medicine and are considered key effectors underlying the therapeutic efficacy of autologous fat grafting for scarring and skin fibrosis, yet clinical outcomes remain variable. This review examines how obesity alters the adipose microenvironment through [...] Read more.
Adipose-derived stem cells (ADSCs) are widely used in regenerative medicine and are considered key effectors underlying the therapeutic efficacy of autologous fat grafting for scarring and skin fibrosis, yet clinical outcomes remain variable. This review examines how obesity alters the adipose microenvironment through chronic inflammation and metabolic dysfunction, resulting in epigenetic changes, mitochondrial impairment, oxidative stress, and premature cellular senescence in ADSCs. ADSCs from obese individuals exhibit reduced stemness, impaired differentiation, and a pro-inflammatory secretome with diminished regenerative capacity. While weight loss may partially reverse these effects, persistent epigenetic and functional memory limits full recovery. This review argues that donor metabolic status is a determinant of ADSC therapeutic potency and discusses key challenges and opportunities for improving regenerative outcomes. Full article
(This article belongs to the Special Issue Stem Cells in Action: Unlocking the Potential of Next-Generation Therapies)
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24 pages, 9102 KB  
Review
Research Landscape of Stem Cell Applications in Musculoskeletal Tissue: A Scoping Review
by Aiyarin Kittilukkana, Puwapong Nimkingratana, Dumnoensun Pruksakorn, Mingkwan Na Takuathung and Nut Koonrungsesomboon
Cells 2026, 15(5), 456; https://doi.org/10.3390/cells15050456 - 4 Mar 2026
Cited by 1 | Viewed by 1285
Abstract
Stem cell therapy represents an intrinsic part of regenerative medicine, with expanding applications in orthopedic and musculoskeletal research. Although studies span from small-animal models to early-phase clinical trials, the field remains fragmented, with wide variation in stem cell types, delivery methods, and target [...] Read more.
Stem cell therapy represents an intrinsic part of regenerative medicine, with expanding applications in orthopedic and musculoskeletal research. Although studies span from small-animal models to early-phase clinical trials, the field remains fragmented, with wide variation in stem cell types, delivery methods, and target tissues. A consolidated overview is needed to inform future directions and bridge the gap between preclinical promise and clinical application. This scoping review synthesized evidence from 500 preclinical and clinical studies, identified through systematic searches and screened in accordance with PRISMA-ScR guidelines. Data were extracted on stem cell type and source, delivery approach, targeted tissue and organ, and disease indication. We found that autologous bone marrow-derived mesenchymal stem cells were the most used, with adipose- and perinatal-derived cells gaining prominence in recent years. Small-animal models such as rats and rabbits predominated, while large-animal and human studies focused mainly on knee osteoarthritis. Intra-articular injection was the principal delivery method across both preclinical and clinical settings. By mapping prevailing practices and emerging trends, this review provides a comprehensive reference for researchers, clinicians, and regulatory stakeholders. It highlights translational pathways, identifies critical gaps, and offers evidence to guide the design of safe, effective, and scalable regenerative therapies in orthopedics. Full article
(This article belongs to the Special Issue Stem Cells in Action: Unlocking the Potential of Next-Generation Therapies)
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27 pages, 2345 KB  
Review
Limbal Epithelial Stem Cells in Review: Immune and Lymphangiogenic Privilege and Their Clinical Relevance
by Berbang Meshko, Thomas Volatier, Claus Cursiefen and Maria Notara
Cells 2026, 15(1), 91; https://doi.org/10.3390/cells15010091 - 5 Jan 2026
Viewed by 2610
Abstract
The cornea maintains transparency by preserving immune and (lymph)angiogenic privilege through active suppression of inflammation and vascular invasion, a process centrally regulated by limbal epithelial stem cells (LESCs) located at the corneoscleral junction. Beyond renewing the corneal epithelium, LESCs maintain immune and vascular [...] Read more.
The cornea maintains transparency by preserving immune and (lymph)angiogenic privilege through active suppression of inflammation and vascular invasion, a process centrally regulated by limbal epithelial stem cells (LESCs) located at the corneoscleral junction. Beyond renewing the corneal epithelium, LESCs maintain immune and vascular balance via extracellular matrix interactions and paracrine signalling, exerting predominantly anti-inflammatory and anti-(lymph)angiogenic effects in vivo. Disruption of the limbal niche by trauma, UV exposure, or genetic disorders such as aniridia leads to limbal stem cell deficiency (LSCD), chronic inflammation, loss of corneal avascularity, and vision loss. The identification of ABCB5 as a key LESC marker has clarified functional limbal subsets, highlighting ABCB5+ epithelial cells as mediators of repair, remodelling, and immune suppression, and positioning them as promising therapeutic targets for treatments that restore both epithelial integrity and corneal immune privilege. Full article
(This article belongs to the Special Issue Stem Cells in Action: Unlocking the Potential of Next-Generation Therapies)
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