International Journal of Molecular Sciences

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5 pages, 179 KiB

Open AccessEditorial

Mesenchymal Stem/Progenitor Cells and Their Derivates in Tissue Regeneration—Part II

by Aleksandra Klimczak

Int. J. Mol. Sci. 2024, 25(9), 4937; https://doi.org/10.3390/ijms25094937 - 30 Apr 2024

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Abstract

During the last three decades, mesenchymal stem/stromal cells (MSCs) were extensively studied, and are mainly considered within the setting of their regenerative and immunomodulatory properties in tissue regeneration [...] Full article

(This article belongs to the Special Issue Mesenchymal Stem/Progenitor Cells and Their Derivates in Tissue Regeneration - Part II)

Research

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20 pages, 9081 KiB

Open AccessArticle

Osteogenic Potential of Human Dental Pulp Stem Cells (hDPSCs) Growing on Poly L-Lactide-Co-Caprolactone and Hyaluronic Acid (HYAFF-11^TM) Scaffolds

by Julia K. Bar, Anna Lis-Nawara, Tomasz Kowalczyk, Piotr G. Grelewski, Sandra Stamnitz, Hanna Gerber and Aleksandra Klimczak

Int. J. Mol. Sci. 2023, 24(23), 16747; https://doi.org/10.3390/ijms242316747 - 25 Nov 2023

Cited by 3 | Viewed by 1288

Abstract

Bone tissue engineering using different scaffolds is a new therapeutic approach in regenerative medicine. This study explored the osteogenic potential of human dental pulp stem cells (hDPSCs) grown on a hydrolytically modified poly(L-lactide-co-caprolactone) (PLCL) electrospun scaffold and a non-woven hyaluronic acid (HYAFF-11™) mesh. [...] Read more.

Bone tissue engineering using different scaffolds is a new therapeutic approach in regenerative medicine. This study explored the osteogenic potential of human dental pulp stem cells (hDPSCs) grown on a hydrolytically modified poly(L-lactide-co-caprolactone) (PLCL) electrospun scaffold and a non-woven hyaluronic acid (HYAFF-11™) mesh. The adhesion, immunophenotype, and osteogenic differentiation of hDPSCs seeded on PLCL and HYAFF-11™ scaffolds were analyzed. The results showed that PLCL and HYAFF-11™ scaffolds significantly supported hDPSCs adhesion; however, hDPSCs’ adhesion rate was significantly higher on PLCL than on HYAFF-11™. SEM analysis confirmed good adhesion of hDPSCs on both scaffolds before and after osteogenesis. Alizarin red S staining showed mineral deposits on both scaffolds after hDPSCs osteogenesis. The mRNA levels of runt-related transcription factor 2 (Runx2), collagen type I (Coll-I), osterix (Osx), osteocalcin (Ocn), osteopontin (Opn), bone sialoprotein (Bsp), and dentin sialophosphoprotein (Dspp) gene expression and their proteins were higher in hDPSCs after osteogenic differentiation on both scaffolds compared to undifferentiated hDPSCs on PLCL and HYAFF-11™. These results showed that PLCL scaffolds provide a better environment that supports hDPSCs attachment and osteogenic differentiation than HYAFF-11™. The high mRNA of early osteogenic gene expression and mineral deposits observed after hDPSCs osteogenesis on a PLCL mat indicated its better impact on hDPSCs’ osteogenic potential than that of HYAFF-11™, and hDPSC/PLCL constructs might be considered in the future as an innovative approach to bone defect repair. Full article

(This article belongs to the Special Issue Mesenchymal Stem/Progenitor Cells and Their Derivates in Tissue Regeneration - Part II)

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23 pages, 3468 KiB

Open AccessArticle

Mesenchymal Stem Cell Conditioned Medium Modulates Inflammation in Tenocytes: Complete Conditioned Medium Has Superior Therapeutic Efficacy than Its Extracellular Vesicle Fraction

by Robert Soukup, Iris Gerner, Thomas Mohr, Sinan Gueltekin, Johannes Grillari and Florien Jenner

Int. J. Mol. Sci. 2023, 24(13), 10857; https://doi.org/10.3390/ijms241310857 - 29 Jun 2023

Cited by 4 | Viewed by 2112

Abstract

Tendinopathy, a prevalent overuse injury, lacks effective treatment options, leading to a significant impact on quality of life and socioeconomic burden. Mesenchymal stem/stromal cells (MSCs) and their secretome, including conditioned medium (CM) and extracellular vesicles (EVs), have shown promise in tissue regeneration and [...] Read more.

Tendinopathy, a prevalent overuse injury, lacks effective treatment options, leading to a significant impact on quality of life and socioeconomic burden. Mesenchymal stem/stromal cells (MSCs) and their secretome, including conditioned medium (CM) and extracellular vesicles (EVs), have shown promise in tissue regeneration and immunomodulation. However, it remains unclear which components of the secretome contribute to their therapeutic effects. This study aimed to compare the efficacy of CM, EVs, and the soluble protein fraction (PF) in treating inflamed tenocytes. CM exhibited the highest protein and particle concentrations, followed by PF and EVs. Inflammation significantly altered gene expression in tenocytes, with CM showing the most distinct separation from the inflamed control group. Treatment with CM resulted in the most significant differential gene expression, with both upregulated and downregulated genes related to inflammation and tissue regeneration. EV treatment also demonstrated a therapeutic effect, albeit to a lesser extent. These findings suggest that CM holds superior therapeutic efficacy compared with its EV fraction alone, emphasizing the importance of the complete secretome in tendon injury treatment. Full article

(This article belongs to the Special Issue Mesenchymal Stem/Progenitor Cells and Their Derivates in Tissue Regeneration - Part II)

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18 pages, 7978 KiB

Open AccessArticle

Evaluation of Changes in Some Functional Properties of Human Mesenchymal Stromal Cells Induced by Low Doses of Ionizing Radiation

by Daria Yu. Usupzhanova, Tatiana A. Astrelina, Irina V. Kobzeva, Yulia B. Suchkova, Vitaliy A. Brunchukov, Anna A. Rastorgueva, Victoria A. Nikitina and Alexander S. Samoilov

Int. J. Mol. Sci. 2023, 24(7), 6346; https://doi.org/10.3390/ijms24076346 - 28 Mar 2023

Viewed by 1382

Abstract

Each person is inevitably exposed to low doses of ionizing radiation (LDIR) throughout their life. The research results of LDIR effects are ambiguous and an accurate assessment of the risks associated with the influence of LDIR is an important task. Mesenchymal stromal cells [...] Read more.

Each person is inevitably exposed to low doses of ionizing radiation (LDIR) throughout their life. The research results of LDIR effects are ambiguous and an accurate assessment of the risks associated with the influence of LDIR is an important task. Mesenchymal stromal cells (MSCs) are the regenerative reserve of an adult organism; because of this, they are a promising model for studying the effects of LDIR. The qualitative and quantitative changes in their characteristics can also be considered promising criteria for assessing the risks of LDIR exposure. The MSCs from human connective gingiva tissue (hG-MSCs) were irradiated at doses of 50, 100, 250, and 1000 mGy by the X-ray unit RUST-M1 (Russia). The cells were cultured continuously for 64 days after irradiation. During the study, we evaluated the secretory profile of hG-MSCs (IL-10, IDO, IL-6, IL-8, VEGF-A) using an ELISA test, the immunophenotype (CD45, CD34, CD90, CD105, CD73, HLA-DR, CD44) using flow cytometry, and the proliferative activity using the xCelligence RTCA cell analyzer at the chosen time points. The results of study have indicated the development of stimulating effects in the early stages of cultivation after irradiation using low doses of X-ray radiation. On the contrary, the effects of the low doses were comparable with the effects of medium doses of X-ray radiation in the long-term periods of cultivation after irradiation and have indicated the inhibition of the functional activity of MSCs. Full article

(This article belongs to the Special Issue Mesenchymal Stem/Progenitor Cells and Their Derivates in Tissue Regeneration - Part II)

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22 pages, 5710 KiB

Open AccessArticle

Do Extracellular Vesicles Derived from Mesenchymal Stem Cells Contain Functional Mitochondria?

by Ljubava D. Zorova, Sergei I. Kovalchuk, Vasily A. Popkov, Valery P. Chernikov, Anastasia A. Zharikova, Anastasia A. Khutornenko, Savva D. Zorov, Konstantin S. Plokhikh, Roman A. Zinovkin, Ekaterina A. Evtushenko, Valentina A. Babenko, Irina B. Pevzner, Yulia A. Shevtsova, Kirill V. Goryunov, Egor Y. Plotnikov, Denis N. Silachev, Gennady T. Sukhikh and Dmitry B. Zorov

Int. J. Mol. Sci. 2022, 23(13), 7408; https://doi.org/10.3390/ijms23137408 - 3 Jul 2022

Cited by 25 | Viewed by 3989

Abstract

Extracellular vesicles (EV) derived from stem cells have become an effective complement to the use in cell therapy of stem cells themselves, which has led to an explosion of research into the mechanisms of vesicle formation and their action. There is evidence demonstrating [...] Read more.

Extracellular vesicles (EV) derived from stem cells have become an effective complement to the use in cell therapy of stem cells themselves, which has led to an explosion of research into the mechanisms of vesicle formation and their action. There is evidence demonstrating the presence of mitochondrial components in EV, but a definitive conclusion about whether EV contains fully functional mitochondria has not yet been made. In this study, two EV fractions derived from mesenchymal stromal stem cells (MSC) and separated by their size were examined. Flow cytometry revealed the presence of mitochondrial lipid components capable of interacting with mitochondrial dyes MitoTracker Green and 10-nonylacridine orange; however, the EV response to the probe for mitochondrial membrane potential was negative. Detailed analysis revealed components from all mitochondria compartments, including house-keeping mitochondria proteins and DNA as well as energy-related proteins such as membrane-localized proteins of complexes I, IV, and V, and soluble proteins from the Krebs cycle. When assessing the functional activity of mitochondria, high variability in oxygen consumption was noted, which was only partially attributed to mitochondrial respiratory activity. Our findings demonstrate that the EV contain all parts of mitochondria; however, their independent functionality inside EV has not been confirmed, which may be due either to the absence of necessary cofactors and/or the EV formation process and, probably the methodology of obtaining EV. Full article

(This article belongs to the Special Issue Mesenchymal Stem/Progenitor Cells and Their Derivates in Tissue Regeneration - Part II)

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Review

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15 pages, 1642 KiB

Open AccessReview

Towards the Standardization of Mesenchymal Stem Cell Secretome-Derived Product Manufacturing for Tissue Regeneration

by Batoul Chouaib, Mandana Haack-Sørensen, Franck Chaubron, Frederic Cuisinier and Pierre-Yves Collart-Dutilleul

Int. J. Mol. Sci. 2023, 24(16), 12594; https://doi.org/10.3390/ijms241612594 - 9 Aug 2023

Cited by 19 | Viewed by 3788

Abstract

Mesenchymal stem cell secretome or conditioned medium (MSC-CM) is a combination of biomolecules and growth factors in cell culture growth medium, secreted by mesenchymal stem cells (MSCs), and the starting point of several derived products. MSC-CM and its derivatives could be applied after [...] Read more.

Mesenchymal stem cell secretome or conditioned medium (MSC-CM) is a combination of biomolecules and growth factors in cell culture growth medium, secreted by mesenchymal stem cells (MSCs), and the starting point of several derived products. MSC-CM and its derivatives could be applied after injuries and could mediate most of the beneficial regenerative effects of MSCs without the possible side effects of using MSCs themselves. However, before the clinical application of these promising biopharmaceuticals, several issues such as manufacturing protocols and quality control must be addressed. This review aims to underline the influence of the procedure for conditioned medium production on the quality of the secretome and its derivatives and highlights the questions considering cell sources and donors, cell expansion, cell passage number and confluency, conditioning period, cell culture medium, microenvironment cues, and secretome-derived product purification. A high degree of variability in MSC secretomes is revealed based on these parameters, confirming the need to standardize and optimize protocols. Understanding how bioprocessing and manufacturing conditions interact to determine the quantity, quality, and profile of MSC-CM is essential to the development of good manufacturing practice (GMP)-compliant procedures suitable for replacing mesenchymal stem cells in regenerative medicine. Full article

(This article belongs to the Special Issue Mesenchymal Stem/Progenitor Cells and Their Derivates in Tissue Regeneration - Part II)

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12 pages, 687 KiB

Open AccessReview

Potency Assays for Mesenchymal Stromal Cell Secretome-Based Products for Tissue Regeneration

by Georgy Sagaradze, Anna Monakova and Anastasia Efimenko

Int. J. Mol. Sci. 2023, 24(11), 9379; https://doi.org/10.3390/ijms24119379 - 27 May 2023

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Abstract

Adult stem cells maintaining tissue homeostasis and regeneration are tightly regulated by their specific microenvironments or stem cell niches. The dysfunction of niche components may alter the activity of stem cells and ultimately lead to intractable chronic or acute disorders. To overcome this [...] Read more.

Adult stem cells maintaining tissue homeostasis and regeneration are tightly regulated by their specific microenvironments or stem cell niches. The dysfunction of niche components may alter the activity of stem cells and ultimately lead to intractable chronic or acute disorders. To overcome this dysfunction, niche-targeting regenerative medicine treatments such as gene, cell, and tissue therapy are actively investigated. Here, multipotent mesenchymal stromal cells (MSCs), and particularly their secretomes, are of high interest due to their potency to recover and reactivate damaged or lost stem cell niches. However, a workflow for the development of MSC secretome-based products is not fully covered by regulatory authorities, and and this issue significantly complicates their clinical translation and has possibly been expressed in a huge number of failed clinical trials. One of the most critical issues in this regard relates to the development of potency assays. In this review, guidelines for biologicals and cell therapies are considered to be applied for the development of potency assays for the MSC secretome-based products that aim for tissue regeneration. Specific attention is paid to their possible effects on stem cell niches and to a spermatogonial stem cell niche in particular. Full article

(This article belongs to the Special Issue Mesenchymal Stem/Progenitor Cells and Their Derivates in Tissue Regeneration - Part II)

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15 pages, 1140 KiB

Open AccessReview

Intraarticular Injections of Mesenchymal Stem Cells in Knee Osteoarthritis: A Review of Their Current Molecular Mechanisms of Action and Their Efficacy

by Emérito Carlos Rodríguez-Merchán

Int. J. Mol. Sci. 2022, 23(23), 14953; https://doi.org/10.3390/ijms232314953 - 29 Nov 2022

Cited by 10 | Viewed by 4539

Abstract

More than 10% of the world’s population suffers from osteoarthritis (OA) of the knee, with a lifetime risk of 45%. Current treatments for knee OA pain are as follows: weight control; oral pharmacological treatment (non-steroidal anti-inflammatory drugs, paracetamol, opioids); mechanical aids (crutches, walkers, [...] Read more.

More than 10% of the world’s population suffers from osteoarthritis (OA) of the knee, with a lifetime risk of 45%. Current treatments for knee OA pain are as follows: weight control; oral pharmacological treatment (non-steroidal anti-inflammatory drugs, paracetamol, opioids); mechanical aids (crutches, walkers, braces, orthotics); therapeutic physical exercise; and intraarticular injections of corticosteroids, hyaluronic acid, and platelet-rich plasma (PRP). The problem is that such treatments usually relieve joint pain for only a short period of time. With respect to intraarticular injections, corticosteroids relieve pain for several weeks, while hyaluronic acid and PRP relieve pain for several months. When the above treatments fail to control knee pain, total knee arthroplasty (TKA) is usually indicated; however, although a very effective surgical technique, it can be associated with medical and postoperative (surgery-related) complications. Therefore, it seems essential to look for safe and effective alternative treatments to TKA. Recently, there has been much research on intraarticular injections of mesenchymal stem cells (MSCs) for the management of OA of the knee joint. This article reviews the latest information on the molecular mechanisms of action of MSCs and their potential therapeutic benefit in clinical practice in patients with painful knee OA. Although most recent publications claim that intraarticular injections of MSCs relieve joint pain in the short term, their efficacy remains controversial given that the existing scientific information on MSCs is indecisive. Before recommending intraarticular MSCs injections routinely in patients with painful knee OA, more studies comparing MSCs with placebo are needed. Furthermore, a standard protocol for intraarticular injections of MSCs in knee OA is needed. Full article

(This article belongs to the Special Issue Mesenchymal Stem/Progenitor Cells and Their Derivates in Tissue Regeneration - Part II)

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