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Fundamental and Practical Perspectives in Regenerative Medicine: Proceedings of the VI National Congress of Regenerative Medicine (2024)

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 15 October 2025 | Viewed by 9150

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Prof. Dr. Vsevolod A. Tkachuk

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1 Institute for Regenerative Medicine, Medical Research and Education Center, Lomonosov Moscow State University, 27/10, Lomonosovsky Ave., 119192 Moscow, Russia
2 Faculty of Medicine, Lomonosov Moscow State University, 27/1, Lomonosovsky Ave., 119192 Moscow, Russia
Interests: regenerative medicine elaboration and implementation of new standards for cell technology applications; biomedical cell and gene therapy product manufacturing, to tissue renewal, vascular growth stimulation and regeneration; stem cell biology, gene therapy and regenerative medicine
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Dr. Pavel Makarevich

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Guest Editor

Institute for Regenerative Medicine, Medical Research and Education Centre, Lomonosov Moscow State University, Moscow 119192, Russia
Interests: regenerative medicine; adult stem cells; cell sheets; tissue engineering; mesenchymal stromal/stem cells
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Special Issue Information

Dear Colleagues,

Advances in regenerative medicine are strongly associated with a multifaceted community of scientists from the fields of medicine, biology, chemistry, physics and other disciplines that explore the nature of the human body’s remarkable ability to support its structure and recover from injury and disease.

This Special Issue aims to collate an innovative selection of cutting-edge reviews and original papers from leading specialists with a special focus on proceedings of the VI National congress of Regenerative Medicine that will be hosted by Moscow University in November 2024. We invite keynote speakers and participants to provide reviews and original articles with a focus on topics including, but not limited to:

Breakthroughs in our understanding of human body cellular renewal and regeneration after injury;
Novel gene, cell therapies and tissue engineering methods to treat human disease (proof-of-concept, pre-clinical and clinical data);
New mechanisms and pathways that regulate responses to injury, healing and its outcomes (e.g., balance of fibrosis and regeneration);
Challenges and prospects in the translational aspects of regenerative medicine (including disease models, manufacture and regulatory issues)

For review papers, please provide a preliminary abstract and title prior to submission.

We grant priority to Congress keynote and invited speakers but shall consider innovative submissions that fit the scope of the Special Issue:

Prof. Dr. Vsevolod A. Tkachuk
Dr. Pavel Makarevich
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. 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

regenerative medicine
stem cell
gene therapy
cell therapy
tissue engineering

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Related Special Issue

Fundamental and Practical Perspectives in Regenerative Medicine: Proceedings of the V National Congress of Regenerative Medicine (2022) in International Journal of Molecular Sciences (25 articles)

Published Papers (8 papers)

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Research

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19 pages, 3181 KiB

Open AccessArticle

Overexpression of BDNF and uPA Combined with the Suppression of Von Hippel–Lindau Tumor Suppressor Enhances the Neuroprotective Activity of the Secretome of Human Mesenchymal Stromal Cells in the Model of Intracerebral Hemorrhage

by Stalik S. Dzhauari, Alexandra L. Primak, Nataliya A. Basalova, Natalia I. Kalinina, Anna O. Monakova, Kirill D. Bozov, Arkadiy Ya. Velichko, Maria E. Illarionova, Olga A. Grigorieva, Zhanna A. Akopyan, Vladimir S. Popov, Pavel G. Malkov, Anastasia Yu. Efimenko, Vsevolod A. Tkachuk and Maxim N. Karagyaur

Int. J. Mol. Sci. 2025, 26(14), 6697; https://doi.org/10.3390/ijms26146697 - 12 Jul 2025

Viewed by 207

Abstract

Nerve tissue damage is an unsolved problem in modern neurology and neurosurgery, which prompts the need to search for approaches to stimulate neuroprotection and regeneration of neural tissue. Earlier we have shown that the secretome of human mesenchymal stromal cells (MSCs) stimulates rat survival, reduces the severity of neurological deficits, and decreases the volume of brain damage in a hemorrhagic stroke model. A significant disadvantage of using the MSC secretome is the need to concentrate it (at least 5–10 fold) to achieve appreciable pharmacological activity. This increases the cost of obtaining clinically applicable amounts of secretome and slows down the clinical translation of this technology. Here, we created a number of genetically modified human MSC cultures, including immortalized MSCs and those with hyperexpression of brain-derived neurotrophic factor (BDNF) and urokinase-type plasminogen activator (uPA) and with suppressed expression of Von Hippel–Lindau tumor suppressor (VHL), and we evaluated the pharmacological activity of their secretomes in a model of intracerebral hemorrhage (ICH) in rats. The secretome of MSCs immortalized by hyperexpression of the catalytic subunit of human telomerase (hTERT) revealed neuroprotective activity indistinguishable from that of primary MSC cultures, yet it still required 10-fold concentration to achieve neuroprotective efficacy. The secretome of MSC culture with combined hyperexpression of BDNF and uPA and suppressed expression of Von Hippel–Lindau tumor suppressor even without additional concentration reduced the severity of neurological disorders and decreased brain lesion volume in the ICH model. The secretomes of MSCs with separate overexpression of BDNF and uPA or suppression of VHL had no such effect or, on the contrary, revealed a toxic effect in the ICH model. Presumably, this may be due to an imbalance in the representation of individual growth factors in the secretome of genetically modified MSCs, which individually may lead to undesirable effects in damaged nervous tissue, such as increased permeability of the blood–brain barrier (under the influence of pro-angiogenic factors) or neural cell apoptosis (due to an excess of neurotrophic factors). The obtained data show that genetic modification of MSC cultures can enhance or alter the therapeutic activity of their secretomes, which can be used in the creation of promising sources of biopharmaceutical substances. Full article

(This article belongs to the Special Issue Fundamental and Practical Perspectives in Regenerative Medicine: Proceedings of the VI National Congress of Regenerative Medicine (2024))

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16 pages, 4784 KiB

Open AccessArticle

In Vitro and In Vivo Testing of Decellularized Lung and Pancreas Matrices as Potential Islet Platforms

by Alexandra Bogomolova, Polina Ermakova, Arseniy Potapov, Artem Mozherov, Julia Tselousova, Ekaterina Vasilchikova, Alexandra Kashina and Elena Zagaynova

Int. J. Mol. Sci. 2025, 26(14), 6692; https://doi.org/10.3390/ijms26146692 - 12 Jul 2025

Viewed by 156

Abstract

The treatment of type 1 diabetes through pancreatic islet transplantation faces significant limitations, including donor organ shortages and poor islet survival due to post-transplantation loss of extracellular matrix support and inadequate vascularization. Developing biocompatible scaffolds that mimic the native islet microenvironment could substantially improve transplantation outcomes. This study aimed to create and evaluate decellularized (DCL) matrices from porcine organs as potential platforms for islet transplantation. Porcine lung and pancreatic tissues were decellularized using four different protocols combining detergents (Triton X-100, SDS and SDC) with optimized incubation times. The resulting matrices were characterized through DNA quantification and histological staining (H&E and Van Gieson). Islet viability was assessed in vitro using Live/Dead staining after 3 and 7 days of culture on the matrices. In vivo biocompatibility was evaluated by implanting matrices into rat omentum or peritoneum, with histological analysis at 1-, 4-, and 8 weeks post-transplantation. Protocols 3 (for lung tissue) and 4 (for pancreas tissue) demonstrated optimal decellularization efficiency with residual DNA levels below 8%, while preserving the collagen and elastin networks. In vitro, islets cultured on decellularized lung matrix had maintained 95% viability by day 7, significantly higher than the controls (60%) and pancreatic matrix (83%). The omentum showed superior performance as an implantation site, exhibiting minimal inflammation and fibrosis compared to the peritoneum sites throughout the 8-week study period. These findings establish DCL as a promising scaffold for islet transplantation due to its superior preservation of ECM components and excellent support of islet viability. This work provides a significant step toward developing effective tissue-engineered therapies for diabetes treatment. Full article

(This article belongs to the Special Issue Fundamental and Practical Perspectives in Regenerative Medicine: Proceedings of the VI National Congress of Regenerative Medicine (2024))

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32 pages, 6617 KiB

Open AccessArticle

Hyaluronan-Containing Injectable Magnesium–Calcium Phosphate Cements Demonstrated Improved Performance, Cytocompatibility, and Ability to Support Osteogenic Differentiation In Vitro

by Natalia S. Sergeeva, Polina A. Krokhicheva, Irina K. Sviridova, Margarita A. Goldberg, Dinara R. Khayrutdinova, Suraya A. Akhmedova, Valentina A. Kirsanova, Olga S. Antonova, Alexander S. Fomin, Ivan V. Mikheev, Aleksander V. Leonov, Pavel A. Karalkin, Sergey A. Rodionov, Sergey M. Barinov, Vladimir S. Komlev and Andrey D. Kaprin

Int. J. Mol. Sci. 2025, 26(14), 6624; https://doi.org/10.3390/ijms26146624 - 10 Jul 2025

Viewed by 255

Abstract

Due to their biocompatibility, biodegradability, injectability, and self-setting properties, calcium–magnesium phosphate cements (MCPCs) have proven to be effective biomaterials for bone defect filling. Two types of MCPC powders based on the magnesium whitlockite or stanfieldite phases with MgO with different magnesium contents (20 and 60%) were synthesised. The effects of magnesium ions (Mg²⁺) on functional properties such as setting time, temperature, mechanical strength, injectability, cohesion, and in vitro degradation kinetics, as well as cytocompatibility in the MG-63 cell line and the osteogenic differentiation of BM hMSCs in vitro, were analysed. The introduction of NaHA into the cement liquid results in an increase in injectability of up to 83%, provides a compressive strength of up to 22 MPa, and shows a reasonable setting time of about 20 min without an exothermic reaction. These cements had the ability to support MG-63 cell adhesion, proliferation, and spread and the osteogenic differentiation of BM hMSCs in vitro, stimulating ALPL, SP7, and RUNX2 gene expression and ALPL production. The combination of the studied physicochemical and biological properties of the developed cement compositions characterises them as bioactive, cytocompatible, and promising biomaterials for bone defect reconstruction. Full article

(This article belongs to the Special Issue Fundamental and Practical Perspectives in Regenerative Medicine: Proceedings of the VI National Congress of Regenerative Medicine (2024))

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15 pages, 2759 KiB

Open AccessArticle

Preconditioning with Rapamycin Improves Therapeutic Potential of Placenta-Derived Mesenchymal Stem Cells in Mouse Model of Hematopoietic Acute Radiation Syndrome

by Vasilii Slautin, Vladislav Ivanov, Alexandr Bugakov, Anna Chernysheva, Ilya Gavrilov, Irina Maklakova, Vladimir Bazarnyi, Dmitry Grebnev and Olga Kovtun

Int. J. Mol. Sci. 2025, 26(10), 4804; https://doi.org/10.3390/ijms26104804 - 17 May 2025

Viewed by 621

Abstract

Acute radiation syndrome (ARS) results from high-dose ionizing radiation (IR) exposure, with bone marrow (BM) being highly susceptible due to its proliferative activity. BM injury causes pancytopenia, leading to infections, anemia, and bleeding. Mesenchymal stem cells (MSCs) hold promise for ARS treatment because of their immunomodulatory, anti-inflammatory, and regenerative properties. However, challenges such as replicative senescence, poor survival, and engraftment in irradiated microenvironments limit their efficacy. This study evaluated rapamycin-preconditioned placenta-derived MSCs (rPD-MSCs) in a mouse ARS model. Rapamycin was selected for preconditioning due to its ability to induce autophagy and modulate cytokine secretion. We assessed rapamycin-dependent modulation of autophagy-related genes and proteins, as well as hematopoietic cytokines secretion in PD-MSCs, and evaluated morphological changes in blood and BM at 7 and 21 days post-irradiation in ICR/CD1 mice. Preconditioning with rapamycin alters the secretion of granulocyte colony-stimulating factor (G-CSF), stem cell factor (SCF), and Fms-related tyrosine kinase 3 ligand (Flt3LG) in PD-MSCs without affecting cell viability. rPD-MSCs better enhance hematopoietic recovery, restore bone marrow cellularity, and increase peripheral blood cell counts by elevating the secretion of hematopoietic cytokines compared to non-preconditioned cells. These results highlight rapamycin preconditioning as a promising strategy to enhance MSCs therapeutic potential for ARS, supporting further preclinical and clinical exploration. Full article

(This article belongs to the Special Issue Fundamental and Practical Perspectives in Regenerative Medicine: Proceedings of the VI National Congress of Regenerative Medicine (2024))

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13 pages, 2648 KiB

Open AccessArticle

Comparative Study of Deep Transfer Learning Models for Semantic Segmentation of Human Mesenchymal Stem Cell Micrographs

by Maksim Solopov, Elizaveta Chechekhina, Anna Kavelina, Gulnara Akopian, Viktor Turchin, Andrey Popandopulo, Dmitry Filimonov and Roman Ishchenko

Int. J. Mol. Sci. 2025, 26(5), 2338; https://doi.org/10.3390/ijms26052338 - 6 Mar 2025

Cited by 2 | Viewed by 1397

Abstract

The aim of this study is to conduct a comparative assessment of the effectiveness of neural network models—U-Net, DeepLabV3+, SegNet and Mask R-CNN—for the semantic segmentation of micrographs of human mesenchymal stem cells (MSCs). A dataset of 320 cell micrographs annotated by cell biology experts was created. The models were trained using a transfer learning method based on ImageNet pre-trained weights. As a result, the U-Net model demonstrated the best segmentation accuracy according to the metrics of the Dice coefficient (0.876) and the Jaccard index (0.781). The DeepLabV3+ and Mask R-CNN models also showed high performance, although slightly lower than U-Net, while SegNet exhibited the least accurate results. The obtained data indicate that the U-Net model is the most suitable for automating the segmentation of MSC micrographs and can be recommended for use in biomedical laboratories to streamline the routine analysis of cell cultures. Full article

(This article belongs to the Special Issue Fundamental and Practical Perspectives in Regenerative Medicine: Proceedings of the VI National Congress of Regenerative Medicine (2024))

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32 pages, 29372 KiB

Open AccessArticle

Transcriptome-Wide Insights: Neonatal Lactose Intolerance Promotes Telomere Damage, Senescence, and Cardiomyopathy in Adult Rat Heart

by Olga V. Anatskaya, Sergei V. Ponomartsev, Artem U. Elmuratov and Alexander E. Vinogradov

Int. J. Mol. Sci. 2025, 26(4), 1584; https://doi.org/10.3390/ijms26041584 - 13 Feb 2025

Viewed by 3906

Abstract

Cardiovascular diseases (CVD) are the primary cause of mortality globally. A significant aspect of CVD involves their association with aging and susceptibility to neonatal programming. These factors suggest that adverse conditions during neonatal development can disrupt cardiomyocyte differentiation, thereby leading to heart dysfunction. This study focuses on the long-term effects of inflammatory and oxidative stress due to neonatal lactose intolerance (NLI) on cardiomyocyte transcriptome and phenotype. Our recent bioinformatic study focused on toggle genes indicated that NLI correlates with the switch off of some genes in thyroid hormone, calcium, and antioxidant signaling pathways, alongside the switch-on/off genes involved in DNA damage response and inflammation. In the presented study, we evaluated cardiomyocyte ploidy in different regions of the left ventricle (LV), complemented by a transcriptomic analysis of genes with quantitative (gradual) difference in expression. Cytophotometric and morphologic analyses of LV cardiomyocytes identified hyperpolyploidy and bridges between nuclei suggesting telomere fusion. Transcriptomic profiling highlighted telomere damage, aging, and chromatin decompaction, along with the suppression of pathways governing muscle contraction and energy metabolism. Echocardiography revealed statistically significant LV dilation and a decrease in ejection fraction. The estimation of survival rates indicated that NLI shortened the median lifespan by approximately 18% (p < 0.0001) compared with the control. Altogether, these findings suggest that NLI may increase susceptibility to cardiovascular diseases by accelerating aging due to oxidative stress and increased telomere DNA damage, leading to hyperpolyploidization and reduced cardiac contractile function. Collectively, our data emphasize the importance of the early identification and management of neonatal inflammatory and metabolic stressors, such as NLI, to mitigate long-term cardiovascular risks. Full article

(This article belongs to the Special Issue Fundamental and Practical Perspectives in Regenerative Medicine: Proceedings of the VI National Congress of Regenerative Medicine (2024))

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Review

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55 pages, 1435 KiB

Open AccessReview

Induced Pluripotent (iPSC) and Mesenchymal (MSC) Stem Cells for In Vitro Disease Modeling and Regenerative Medicine

by Egor Panferov, Maria Dodina, Vasiliy Reshetnikov, Anastasia Ryapolova, Roman Ivanov, Alexander Karabelsky and Ekaterina Minskaia

Int. J. Mol. Sci. 2025, 26(12), 5617; https://doi.org/10.3390/ijms26125617 - 11 Jun 2025

Viewed by 943

Abstract

In vitro disease modeling can be used both for understanding the development of pathology and for screening various therapies, such as gene therapies. This approach decreases costs, shortens research timelines, reduces animal testing, and may be more accurate in replicating the disease phenotype compared to animal models. This review focuses on the two types of stem cells: induced pluripotent stem cells (iPSCs) and mesenchymal stem cells (MSCs), which can be used for this purpose. Special attention is given to the impact of the isolation source and the variable expression of certain phenotypic markers on the differentiation capacity of these cells. Both similarities and critical differences between iPSCs and MSCs, as well as the outcomes of past and ongoing clinical trials, are discussed in order to gain insight and understanding as to which of these two cell types can be more suitable for the particular biomedical application. Full article

(This article belongs to the Special Issue Fundamental and Practical Perspectives in Regenerative Medicine: Proceedings of the VI National Congress of Regenerative Medicine (2024))

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18 pages, 704 KiB

Open AccessReview

The Problem of Molecular Target Choice for CAR-T Cells in Acute Myeloid Leukemia Therapy

by Varvara Maiorova, Murad D. Mollaev, Polina Vikhreva, Alexey Kibardin, Michael A. Maschan and Sergey S. Larin

Int. J. Mol. Sci. 2025, 26(12), 5428; https://doi.org/10.3390/ijms26125428 - 6 Jun 2025

Viewed by 690

Abstract

Recently, the chimeric antigen receptor (CAR)-T approach represented a breakthrough in the treatment of B-cell malignancies, encouraging the application of the approach for other hematological diseases, such as acute myeloid leukemia (AML). Heterogeneity and antigen variation in the pathological cell population hinder the choice of molecular targets in the case of AML. In this review, the critical aspects were described that are usually considered when selecting molecular targets for the new CAR genetic constructs. The role of AML-associated antigens in AML progression was covered. In conclusion, we proposed an approach that may allow the elimination of pathological cells in AML more effectively. Full article

(This article belongs to the Special Issue Fundamental and Practical Perspectives in Regenerative Medicine: Proceedings of the VI National Congress of Regenerative Medicine (2024))

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