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Recent Advances in Adult Stem Cell Research
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Recent Advances in Adult Stem Cell Research

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

Deadline for manuscript submissions: 20 January 2026 | Viewed by 4147

Special Issue Editor

Dr. Dongsu Park

E-Mail Website
Guest Editor
Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA
Interests: skeletal stem cells; tendon stem/progenitor cells; hematopoietic stem cells; stem cell microenvironment; tissue regeneration; stem cell imaging

Special Issue Information

Dear Colleagues,

Tissue-resident stem cells are multipotent cells found in a wide variety of fetal and adult tissues capable of differentiating into various lineages and are critical for their own tissue maintenance and function. Since their discovery, tissue-resident stem cells have been shown to possess remarkable potential for therapeutic applications, which is reflected by a rapid increase in clinical trials targeting stem cells for the treatment of a broad spectrum of diseases. However, much has remained unknown about adult stem cell biology, and challenges remain in their tissue regulatory mechanism and functional changes in aging. We welcome manuscripts of any article type investigating the stem cell-mediated homeostatic or repair mechanisms of multiple tissues damaged by trauma, such as bone/bone marrow, muscle, cartilage, and skin. In addition, we welcome original research investigating the importance of the communication between the physical microenvironment and stem cells in the application of tissue regeneration and repair strategies.

Dr. Dongsu Park
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.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • tissue-resident stem cells
  • skeletal stem/progenitor cells
  • hematopoietic stem cells
  • tendon/ligament stem cells
  • musculoskeletal tissue regeneration
  • stem cell microenvironment
  • stem cell aging

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Published Papers (4 papers)

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Research

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16 pages, 10226 KB  
Article
Distinct Intrinsic and Extrinsic Factors Differentially Regulate Skeletal Stem Cells in Calvaria Versus Long Bones During Bone Regeneration
by Jea Solidum, Kohei Yamasaki, Youngjae Jeong, Laura Ortinau, Francisco Heralde III and Dongsu Park
Int. J. Mol. Sci. 2025, 26(19), 9413; https://doi.org/10.3390/ijms26199413 - 26 Sep 2025
Viewed by 383
Abstract
Calvarial suture skeletal stem cells (Su-SSCs) are a distinct stem cell population for craniofacial bone formation by intramembranous ossification, compared to long bone periosteal SSCs (LB-PSSCs) with endochondral (osteochondrogenic) ossification. However, whether SSC intrinsic or extrinsic factors affect their differentiation process has not [...] Read more.
Calvarial suture skeletal stem cells (Su-SSCs) are a distinct stem cell population for craniofacial bone formation by intramembranous ossification, compared to long bone periosteal SSCs (LB-PSSCs) with endochondral (osteochondrogenic) ossification. However, whether SSC intrinsic or extrinsic factors affect their differentiation process has not been well elucidated. Here, using an inducible Prx1-CreER-EGFP+/−;Rosa26-tdTomato mouse model, we observed that endogenous Prx1+ Su-SSCs and their orthotopic transplantation into calvarial injury do not form cartilage intermediates at the injury sites, while the transplantation of Prx1+ LB-PSSCs into LB injury induces osteochondrogenic differentiation, respectively. However, the heterotopic transplantation of Prx1+ Su-SSCs (Su-SSCs into LB injury) showed some surprising findings that the transplanted Su-SSCs acquire new chondrocyte differentiation properties at the LB injury sites, although the heterotopic-transplanted Prx1+ LB-PSSCs maintained their endochondral ossification properties at the calvarial injury sites. Further, a comparative single-cell transcriptomic analysis of LB-PSSCs and Su-SSCs revealed that Su-SSCs express a higher set of anti-chondrogenic genes, such as Wnt5b, Twist1 while LB-PSSCs highly express chondrogenic Hoxa-9, Hoxc-9, Hoxa-10, Hoxc-10, and Comp genes. We also found that the heterotopic transplantation of LB-PSSCs into calvarial injury enhances bone healing in vivo. Taken together, these findings suggest that LB-PSSCs have high regenerative capability with invariable endochondral ossification even after the heterotopic transplantation but Su-SSCs are more flexible and regulated by the local bone environment. The transplantation of periosteal SSCs will be a promising method for large craniofacial bone defects. Full article
(This article belongs to the Special Issue Recent Advances in Adult Stem Cell Research)
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20 pages, 10915 KB  
Article
Combination Therapy with Human Chorionic Villi MSCs and Secretory Factors Enhances Cutaneous Wound Healing in a Rat Model
by Qingwen Deng, Jiawei Huang, Lai Ling Tsang, Jinghui Guo, Chi Chiu Wang, Xiaohu Zhang and Xiaohua Jiang
Int. J. Mol. Sci. 2025, 26(14), 6888; https://doi.org/10.3390/ijms26146888 - 17 Jul 2025
Viewed by 810
Abstract
Cutaneous wound healing is a complex process involving multiple cellular and molecular events, and current treatments often face limitations in efficacy and safety. Stem-cell therapy, particularly using mesenchymal stem cells (MSCs), has emerged as a promising approach to enhance wound repair through both [...] Read more.
Cutaneous wound healing is a complex process involving multiple cellular and molecular events, and current treatments often face limitations in efficacy and safety. Stem-cell therapy, particularly using mesenchymal stem cells (MSCs), has emerged as a promising approach to enhance wound repair through both direct cell replacement and paracrine signaling. This study investigates the therapeutic potential of human chorionic villus mesenchymal stem cells (hCV-MSCs) and their secretory factors in enhancing cutaneous wound healing. Utilizing a rat model, we combined the local administration of hCV-MSC-laden PEGDA/SA/Col-I hydrogel with the systemic delivery of their secretome, aiming to leverage the complementary mechanisms of cellular and cell-free therapies. Our findings demonstrate that hCV-MSCs delivered via PEGDA/SA/Col-I hydrogel significantly accelerated wound closure compared to controls, with near-complete closure observed by day 20. Histological analysis revealed enhanced keratinocyte maturation (increased KRT10/KRT14 ratio) and a higher density of CD31+ blood vessels, indicating improved re-epithelialization and angiogenesis. A mass spectrometry analysis of the hCV-MSC secretome identified 849 proteins, with enrichment in pathways related to ECM organization, cell adhesion, and immune regulation. Key proteins such as ANXA1, SERPINE1, and WNT5A were implicated in wound-healing processes. Combination therapy with systemic secretome administration further accelerated wound closure and enhanced collagen deposition, keratinocyte maturation, and vascularization compared to hCV-MSCs alone. Our results highlight the promising application of hCV-MSCs and their secretome in cutaneous wound healing, paving the way for innovative therapeutic strategies that integrate both local and systemic regenerative approaches. Full article
(This article belongs to the Special Issue Recent Advances in Adult Stem Cell Research)
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Review

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15 pages, 1394 KB  
Review
Growth Plate Skeletal Stem Cells and Their Actions Within the Stem Cell Niche
by Natalie Kiat-amnuay Cheng, Shion Orikasa and Noriaki Ono
Int. J. Mol. Sci. 2025, 26(19), 9460; https://doi.org/10.3390/ijms26199460 - 27 Sep 2025
Viewed by 1111
Abstract
The growth plate is a specialized cartilage structure near the ends of long bones that orchestrates longitudinal bone growth during fetal and postnatal stages. Within this region reside a dynamic population of growth plate skeletal stem cells (gpSSCs), primarily located in the resting [...] Read more.
The growth plate is a specialized cartilage structure near the ends of long bones that orchestrates longitudinal bone growth during fetal and postnatal stages. Within this region reside a dynamic population of growth plate skeletal stem cells (gpSSCs), primarily located in the resting zone, which possess self-renewal and multilineage differentiation capacity. Recent advances in cell-lineage tracing, single-cell transcriptomics, and in vivo functional studies have revealed distinct subpopulations of gpSSCs, which are defined by markers such as parathyroid hormone-related protein (PTHrP), CD73, axis inhibition protein 2 (Axin2), forkhead box protein A2 (FoxA2), and apolipoprotein E (ApoE). These stem cells interact intricately with their niche, particularly after the formation of the secondary ossification center, through stage-specific regulatory mechanisms involving several key signaling pathways. This review summarizes the current understanding of gpSSC identity, behavior, and regulation, focusing on how these cells sustain growth plate function through adapting to biomechanical and molecular cues. Full article
(This article belongs to the Special Issue Recent Advances in Adult Stem Cell Research)
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21 pages, 2396 KB  
Review
Co-Culture Approaches in Cartilage and Bone Tissue Regeneration
by Iwona Deszcz and Julia Bar
Int. J. Mol. Sci. 2025, 26(12), 5711; https://doi.org/10.3390/ijms26125711 - 14 Jun 2025
Viewed by 1346
Abstract
Cartilage and bone defects as well as osteoarthritis are prevalent worldwide, affecting individuals across all age groups, from young, active populations to older adults. The standard protocol in cartilage regeneration involves knee replacement surgery through the implantation of an endoprosthesis. Current clinical protocols [...] Read more.
Cartilage and bone defects as well as osteoarthritis are prevalent worldwide, affecting individuals across all age groups, from young, active populations to older adults. The standard protocol in cartilage regeneration involves knee replacement surgery through the implantation of an endoprosthesis. Current clinical protocols involving cell-based therapies are associated with limitations, including the lack of functional cartilage-like tissue and dedifferentiation of chondrocyte, particularly during monoculture. Similarly, in bone regeneration, the “gold standard” is the use of bone auto- or allografts, which are associated with immunological rejection, inadequate vascularization, and limited osteogenesis. To overcome these limitations, various co-culture techniques have been introduced as promising strategies for cartilage and bone tissue regeneration. These systems aim to mimic native microenvironments by promoting interactions between chondrocytes and mesenchymal stromal cells (MSCs) in cartilage repair and between osteogenic and angiogenic cells in bone regeneration. This paper introduces different co-culture systems focusing on in vitro crosstalk between MSCs derived from various sources and other somatic cell populations in cartilage and bone regeneration. Full article
(This article belongs to the Special Issue Recent Advances in Adult Stem Cell Research)
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