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Pharmaceutics
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Mesenchymal Stromal Cell-Based Cell Therapy: Recent Advances and Expectations
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Mesenchymal Stromal Cell-Based Cell Therapy: Recent Advances and Expectations

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Gene and Cell Therapy".

Deadline for manuscript submissions: closed (31 July 2025) | Viewed by 5387

Special Issue Editors

Dr. Paola Chiodelli

E-Mail Website
Guest Editor
Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
Interests: angiogenesis; cancer biology; spheroids; mesenchymal stromal cells; cancer associated fibroblasts; perinatal derivatives
Special Issues, Collections and Topics in MDPI journals
Dr. Andrea Papait

E-Mail Website
Guest Editor
Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
Interests: immunomodulation; mesenchymal stromal cells; cancer biology; regenerative medicine; immunology; perinatal derivatives; secretoma; extracellular vesicles
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Mesenchymal stromal cells (MSCs) can be derived from various human tissues and organs. These cells exhibit a multipotent differentiation capacity in vitro. Although this characteristic has made them appealing for regenerative medicine applications due to their potential to regenerate damaged tissue, it has been observed over the years that the true therapeutic effect of these cells is associated with their paracrine action, particularly their ability to modulate the surrounding microenvironment, thereby promoting tissue homeostasis restoration. Numerous in vitro and in vivo studies have demonstrated that the secretome of MSCs, comprising the factors produced and released by these cells, including proteins, lipids, extracellular vesicles, and other factors, plays a pivotal role not only in the context of regenerative medicine but also in the tumor microenvironment. Through their immunomodulatory action, MSCs can contribute to the tumor's immune evasion mechanism.

Indeed, various components released by MSCs, particularly extracellular vesicles, among the factors responsible for their paracrine action, play a significant role in modulating the tumor microenvironment and influencing tumor development. Recent studies have specifically highlighted the critical involvement of mesenchymal stromal cell-derived exosomes (MSC-derived exosomes) in cancer resistance to chemotherapy agents, targeted therapy drugs, radiotherapy, and immunotherapy.

We invite original research and review articles that can contribute to the advancement of knowledge and discussion on two aspects of MSC paracrine activity:

  1. The ability to exert a pro-regenerative action;
  2. The capacity to play a significant role in the tumor microenvironment or potentially act therapeutically in the field of oncology.

Dr. Paola Chiodelli
Dr. Andrea Papait
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 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. Pharmaceutics is an international peer-reviewed open access monthly 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 2900 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

  • cancer
  • exosome
  • mesenchymal stem cell
  • therapy resistance
  • regenerative medicine

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Published Papers (4 papers)

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Research

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25 pages, 2736 KB  
Article
Therapeutic Effects of Intranasal Administration of Mesenchymal Stem Cell-Derived Secretome in Rats Exposed to Chronic Unpredictable Mild Stress
by Alba Ávila, María Eugenia Riveros, Sofía Adasme, Coram Guevara, Rodrigo Del Rio, Fernando C. Ortiz, Nicole Leibold and Fernando Ezquer
Pharmaceutics 2025, 17(9), 1129; https://doi.org/10.3390/pharmaceutics17091129 - 29 Aug 2025
Abstract
Background: Major depression is a significant source of suffering and economic loss. Despite efforts to understand this condition and find better treatments, the burden imposed by this disease continues to rise. Most approved pharmacological treatments for depression focus on controlling the availability [...] Read more.
Background: Major depression is a significant source of suffering and economic loss. Despite efforts to understand this condition and find better treatments, the burden imposed by this disease continues to rise. Most approved pharmacological treatments for depression focus on controlling the availability of monoamines in synapses. However, accumulating evidence suggests that neuroinflammation, oxidative stress, and reduced hippocampal neurogenesis play key roles as causal factors in the development of major depression symptoms. Therefore, preclinical testing of pharmacological approaches targeting these factors is essential. Mesenchymal stem cells (MSCs) are known for their potential as powerful antioxidants and anti-inflammatory agents, exerting neuroprotective actions in the brain. They produce various therapeutic molecules in a paracrine manner, collectively known as secretome. Methods: In this work, we evaluated the antidepressant potential of repeated intranasal administration of MSC-derived secretome in an animal model of major depressive disorder induced by chronic mild unpredictable stress. Results: We observed that intranasal administration of MSC-derived secretome reduced the appearance of some of the behavioral parameters commonly associated with major depression, including anhedonic, apathetic, and anxious behaviors, inducing a strong reduction in the overall depression score compared to vehicle-treated animals. At the structural level, secretome administration prevented increased astrocyte density and the atrophy of astrocyte processes observed in vehicle-treated stressed animals. Additionally, secretome administration induced an increase in myelin levels and oligodendroglia in the cortex. Conclusions: Our data suggests that intranasal administration of MSC-derived secretome may represent a potential therapeutic alternative to current treatments for this devastating pathology. Full article
(This article belongs to the Special Issue Mesenchymal Stromal Cell-Based Cell Therapy: Recent Advances and Expectations)
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18 pages, 2876 KB  
Article
The Secretome of Human Deciduous Tooth-Derived Mesenchymal Stem Cells Enhances In Vitro Wound Healing and Modulates Inflammation
by Thais Simião Payão, Vanessa Pellegrini, Joseane Morari, Gisele Mara Silva Gonçalves, Maria Carolina Ximenes de Godoy, Alessandra Gambero, Leonardo O. Reis, Lício Augusto Velloso, Eliana Pereira Araújo and Lívia Bitencourt Pascoal
Pharmaceutics 2025, 17(8), 961; https://doi.org/10.3390/pharmaceutics17080961 - 25 Jul 2025
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Abstract
Background/Objectives: Chronic wounds represent a significant clinical and public health challenge due to impaired tissue repair and high associated morbidity. This study investigates the therapeutic potential of the secretome derived from human mesenchymal stem cells obtained from the pulp of deciduous teeth (hDP-MSCs) [...] Read more.
Background/Objectives: Chronic wounds represent a significant clinical and public health challenge due to impaired tissue repair and high associated morbidity. This study investigates the therapeutic potential of the secretome derived from human mesenchymal stem cells obtained from the pulp of deciduous teeth (hDP-MSCs) in promoting skin wound healing. Methods: After confirming the mesenchymal identity and multipotent differentiation potential of hDP-MSCs by using flow cytometry and histological staining, the effects of the secretome on human keratinocyte (HaCaT) cultures were evaluated. Results: Scratch assays, performed under high- and low-glucose conditions, demonstrated that the secretome significantly promoted keratinocyte migration and wound closure without compromising cell viability. Additionally, the secretome modulated the expression of key genes involved in inflammation and tissue regeneration, including IL-1β, TNF-α, TGF-β1, and VEGF-α, in a time-dependent manner. Under inflammatory conditions induced by lipopolysaccharide, co-treatment with the secretome significantly reduced TNF-α expression and increased TGF-β1 expression, suggesting an anti-inflammatory effect. Conclusions: These findings indicate the potential of the hDP-MSC-derived secretome as a promising cell-free therapeutic strategy capable of accelerating skin regeneration and modulating the inflammatory response during the wound healing process. Full article
(This article belongs to the Special Issue Mesenchymal Stromal Cell-Based Cell Therapy: Recent Advances and Expectations)
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Review

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24 pages, 1275 KB  
Review
Emerging Role of Mesenchymal Stromal Cell and Exosome Therapies in Treating Cognitive Impairment
by Vick Key Tew, Muttiah Barathan, Fazlina Nordin, Jia Xian Law and Min Hwei Ng
Pharmaceutics 2025, 17(3), 284; https://doi.org/10.3390/pharmaceutics17030284 - 20 Feb 2025
Cited by 1 | Viewed by 1461
Abstract
Cognitive aging, characterized by the gradual decline in cognitive functions such as memory, attention, and problem-solving, significantly impacts daily life. This decline is often accelerated by neurodegenerative diseases, particularly Alzheimer’s Disease (AD) and Parkinson’s Disease (PD). AD is marked by the accumulation of [...] Read more.
Cognitive aging, characterized by the gradual decline in cognitive functions such as memory, attention, and problem-solving, significantly impacts daily life. This decline is often accelerated by neurodegenerative diseases, particularly Alzheimer’s Disease (AD) and Parkinson’s Disease (PD). AD is marked by the accumulation of amyloid-beta plaques and tau tangles, whereas PD involves the degeneration of dopaminergic neurons. Both conditions lead to severe cognitive impairment, greatly diminishing the quality of life for affected individuals. Recent advancements in regenerative medicine have highlighted mesenchymal stromal cells (MSCs) and their derived exosomes as promising therapeutic options. MSCs possess regenerative, neuroprotective, and immunomodulatory properties, which can promote neurogenesis, reduce inflammation, and support neuronal health. Exosomes, nanosized vesicles derived from MSCs, provide an efficient means for delivering bioactive molecules across the blood–brain barrier, targeting the underlying pathologies of AD and PD. While these therapies hold great promise, challenges such as variability in MSC sources, optimal dosing, and effective delivery methods need to be addressed for clinical application. The development of robust protocols, along with rigorous clinical trials, is crucial for validating the safety and efficacy of MSC and exosome therapies. Future research should focus on overcoming these barriers, optimizing treatment strategies, and exploring the integration of MSC and exosome therapies with lifestyle interventions. By addressing these challenges, MSC- and exosome-based therapies could offer transformative solutions for improving outcomes and enhancing the quality of life for individuals affected by cognitive aging and neurodegenerative diseases. Full article
(This article belongs to the Special Issue Mesenchymal Stromal Cell-Based Cell Therapy: Recent Advances and Expectations)
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24 pages, 1620 KB  
Review
Stem Cell-Derived Extracellular Vesicles in the Treatment of Cardiovascular Diseases
by Jennifer McDonald, Sidhesh Mohak and Zsolt Fabian
Pharmaceutics 2024, 16(3), 381; https://doi.org/10.3390/pharmaceutics16030381 - 11 Mar 2024
Cited by 3 | Viewed by 2594
Abstract
Cardiovascular disease constitutes a noteworthy public health challenge characterized by a pronounced incidence, frequency, and mortality rate, particularly impacting specific demographic groups, and imposing a substantial burden on the healthcare infrastructure. Certain risk factors, such as age, gender, and smoking, contribute to the [...] Read more.
Cardiovascular disease constitutes a noteworthy public health challenge characterized by a pronounced incidence, frequency, and mortality rate, particularly impacting specific demographic groups, and imposing a substantial burden on the healthcare infrastructure. Certain risk factors, such as age, gender, and smoking, contribute to the prevalence of fatal cardiovascular disease, highlighting the need for targeted interventions. Current challenges in clinical practice involve medication complexities, the lack of a systematic decision-making approach, and prevalent drug therapy problems. Stem cell-derived extracellular vesicles stand as versatile entities with a unique molecular fingerprint, holding significant therapeutic potential across a spectrum of applications, particularly in the realm of cardio-protection. Their lipid, protein, and nucleic acid compositions, coupled with their multifaceted functions, underscore their role as promising mediators in regenerative medicine and pave the way for further exploration of their intricate contributions to cellular physiology and pathology. Here, we overview our current understanding of the possible role of stem cell-derived extracellular vesicles in the clinical management of human cardiovascular pathologies. Full article
(This article belongs to the Special Issue Mesenchymal Stromal Cell-Based Cell Therapy: Recent Advances and Expectations)
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