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Stem Cells and Regenerative Medicine: In Vitro and In Vivo Studies—2nd Edition

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: closed (20 September 2025) | Viewed by 6994

Special Issue Editor

Dr. Alessia Peserico

E-Mail Website
Guest Editor
Faculty of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, 64100 Teramo, Italy
Interests: stem cell homing; nanoparticle assisted stem cell tracking; regenerative medicine ovarian follicologenesis in mammals
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In recent years, stem cell therapy has become a very promising and advanced scientific research topic. Stem cells have the capability to self-renew and differentiate into several cell types, and are involved in physiological regeneration processes.

In the context of tissue injury, stem cells have gained worldwide attention because of their immense potential for immunomodulation and their therapeutic function. Stem cells can migrate to tissue injury areas to contribute to immune modulation, secrete anti-inflammatory cytokines and evade the immune system.

With so many stem cell replacement therapies undergoing clinical trials, there is a compelling need to understand the mechanisms behind a successful therapy, and one of the critical points of their discovery is to monitor and manage stem cell migration, proliferation, differentiation and organization in vitro as well as in vivo. In this context, the use of biomaterials to manipulate stem cells providing control of their behavior and homing has received great interest, becoming a pivotal step for the development of innovative stem cell transplantation solutions. 

This Special Issue aims to provide the latest updates on stem cells and their in vitro and in vivo applications in the regenerative medicine field, opening novel and advanced strategies for tissue-repairing processes and many other clinical applications.

Original articles, up-to-date review articles and commentaries addressing this topic are all welcome.

Dr. Alessia Peserico
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

  • stem cells
  • stem cell homing
  • stem cell tracking
  • regeneration
  • tissue injury
  • immunomodulation
  • biomaterials
  • tissue-on-a-chip
  • organoids
  • differentiation

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Related Special Issue

Published Papers (3 papers)

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Research

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20 pages, 2842 KB  
Article
Comparative Regenerative Efficacy of PRP Combined with Chondrocytes or Mesenchymal Stem Cells for Intervertebral Disc Regeneration in a Rabbit Model
by Pedro M. Reyes-Fernandez, Viktor J. Romero-Díaz, Jaime García Juárez, José F. Vílchez-Cavazos, Carlos A. Acosta-Olivo, Víctor M. Peña-Martínez and Jorge Lara-Arias
Int. J. Mol. Sci. 2025, 26(20), 10007; https://doi.org/10.3390/ijms262010007 - 14 Oct 2025
Viewed by 279
Abstract
Intervertebral disc degeneration is a leading cause of chronic back pain, with existing treatments focusing on symptom management rather than true tissue repair. Cellular therapies—such as platelet-rich plasma (PRP), autologous chondrocytes, and mesenchymal stem cells (MSCs)—have emerged as promising strategies for disc regeneration. [...] Read more.
Intervertebral disc degeneration is a leading cause of chronic back pain, with existing treatments focusing on symptom management rather than true tissue repair. Cellular therapies—such as platelet-rich plasma (PRP), autologous chondrocytes, and mesenchymal stem cells (MSCs)—have emerged as promising strategies for disc regeneration. In this study, fifteen New Zealand white rabbits underwent fluoroscopy-guided needle puncture of the L4-L5 discs and were allocated to receive PRP alone, PRP-chondrocytes, or PRP-MSCs eight weeks later, while the L3-L4 disc served as a healthy internal control. At 16 weeks post-injury, histological scoring revealed significant improvements in annular integrity, cellularity, and matrix composition in all treated groups compared with untreated lesions, with the greatest gains observed in the PRP-chondrocytes arm, intermediate effects with PRP-MSCs, and more modest changes with PRP alone. Complementary RT-qPCR analysis of COL2A1 and COL10A1 expression confirmed a shift toward a more regenerative phenotype, marked by enhanced COL2A1 and reduced COL10A1 levels, which was most pronounced in the PRP-chondrocytes arm. Despite these advances, none of the interventions fully restored the healthy disc architecture, underscoring the complexity of disc repair. These findings support the potential of combining PRP with chondrocytes or MSCs for intervertebral disc regeneration and demonstrate the need for further optimization of cell doses, PRP formulations, and delivery protocols before clinical translation. Full article
(This article belongs to the Special Issue Stem Cells and Regenerative Medicine: In Vitro and In Vivo Studies—2nd Edition)
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17 pages, 11550 KB  
Article
Cartilage Regeneration Potential in Early Osteoarthritis of the Knee: A Prospective, Randomized, Open, and Blinded Endpoint Study Comparing Adipose-Derived Mesenchymal Stem Cell (ADSC) Therapy Versus Hyaluronic Acid
by Ponthep Tangkanjanavelukul, Saradej Khuangsirikul, Danai Heebthamai, Montarop Yamabhai, Thitima Sumphanapai, Nattapat Khumtong and Thanainit Chotanaphuti
Int. J. Mol. Sci. 2025, 26(17), 8476; https://doi.org/10.3390/ijms26178476 - 31 Aug 2025
Viewed by 1361
Abstract
Early-stage knee osteoarthritis (knee OA) lacks effective regenerative therapies. This study aimed to compare the cartilage regenerative effects, clinical efficacy, and safety of intra-articular injections of autologous adipose-derived mesenchymal stem cells (ADSCs) versus hyaluronic acid (HA). Forty-eight patients with early knee OA were [...] Read more.
Early-stage knee osteoarthritis (knee OA) lacks effective regenerative therapies. This study aimed to compare the cartilage regenerative effects, clinical efficacy, and safety of intra-articular injections of autologous adipose-derived mesenchymal stem cells (ADSCs) versus hyaluronic acid (HA). Forty-eight patients with early knee OA were enrolled in a prospective open-blinded multi-center study at Suranaree University of Technology Hospital and Phramongkutklao Hospital. Participants were randomized into either the ADSC or HA group. Primary outcomes included MRI-based cartilage lesion volume, synovial thickness via ultrasound, and WOMAC scores over 6 months. MRI results revealed significant and progressive cartilage regeneration in the ADSC group. In particular, medial femoral cartilage lesion volume decreased by 50.06 mm3, whereas the HA group showed an increase of 36.44 mm3. Synovial thickness also declined significantly in the ADSC group at 3 and 6 months. Both groups demonstrated reduced symptoms, but the ADSC group achieved superior and sustained improvements in WOMAC pain, stiffness, and function scores throughout the 6-month follow-up. The clinical benefits were consistent and more pronounced compared with HA. No serious adverse events occurred. In conclusion, intra-articular ADSC injections show superior cartilage restoration on MRI and better clinical outcomes than HA injection, making them a promising treatment for early-stage knee OA. Full article
(This article belongs to the Special Issue Stem Cells and Regenerative Medicine: In Vitro and In Vivo Studies—2nd Edition)
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Review

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20 pages, 1390 KB  
Review
The Hidden Power of the Secretome: Therapeutic Potential on Wound Healing and Cell-Free Regenerative Medicine—A Systematic Review
by Jhon W. Prado-Yupanqui, Lourdes Ramírez-Orrego, Denny Cortez, Victor Juan Vera-Ponce, Stella M. Chenet, Juan R. Tejedo and Rafael Tapia-Limonchi
Int. J. Mol. Sci. 2025, 26(5), 1926; https://doi.org/10.3390/ijms26051926 - 23 Feb 2025
Cited by 7 | Viewed by 4884
Abstract
Various types of wounds represent a persistent healthcare burden that demands innovative and effective therapeutic solutions. Innovative approaches have emerged that focus on skin regeneration with minimal side effects. One such method is cell-free therapy that utilizes the secretome of human mesenchymal stem [...] Read more.
Various types of wounds represent a persistent healthcare burden that demands innovative and effective therapeutic solutions. Innovative approaches have emerged that focus on skin regeneration with minimal side effects. One such method is cell-free therapy that utilizes the secretome of human mesenchymal stem cells (hMSCs) as a promising alternative to traditional cell-based therapies, leveraging a complex mixture of bioactive molecules, including growth factors, cytokines, and extracellular vesicles, to accelerate tissue regeneration. This systematic review synthesizes the findings of 35 studies evaluating the impact of hMSC-derived secretomes on wound healing, with a focus on their regenerative, immunomodulatory, and angiogenic effects. The influence of MSC sources (adipose tissue, bone marrow, umbilical cord) and culture conditions on secretome composition and efficacy in the cutaneous wound healing process is examined, highlighting their therapeutic potential in regenerative medicine. This review also explores emerging preclinical and clinical applications, highlighting promising results, such as enhanced fibroblast proliferation, reduced inflammation, and improved extracellular matrix remodeling. In addition, advances in secretome-based biomaterials, including hydrogels and scaffolds, which optimize therapeutic delivery and efficacy are discussed. Despite the growing body of evidence supporting the safety and efficacy of secretomes, challenges remain regarding standardization, large-scale production, and clinical validation. This review highlights the potential of MSC-derived secretomes as a next-generation cell-free approach for wound healing and regenerative medicine. Full article
(This article belongs to the Special Issue Stem Cells and Regenerative Medicine: In Vitro and In Vivo Studies—2nd Edition)
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