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

Chouaib, Batoul; Haack‐Sørensen, Mandana; Chaubron, Franck; Cuisinier, Frédéric; Collart-Dutilleul, Pierre-Yves

doi:10.3390/ijms241612594

Cited by 16 publications

(9 citation statements)

References 123 publications

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“…GMPs in Stem Cell-Based Therapeutics MSCs must comply with current GMP standards, ensuring their readiness for further manufacturing steps. GMPs, enforced by agencies like the US Food and Drug Administration (FDA), set forth rigorous rules to guarantee that products are consistently produced and controlled according to quality standards [201]. Adherence to GMP standards is a fundamental requirement for obtaining marketing authorization for stem cell-based therapeutics [202].…”

Section: Mechanobiologically Mediated Differentiation Of Stem Cellsmentioning

confidence: 99%

Emerging Strategies in Mesenchymal Stem Cell-Based Cardiovascular Therapeutics

Kumar,

Mishra,

Tran

et al. 2024

Cells

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Cardiovascular diseases continue to challenge global health, demanding innovative therapeutic solutions. This review delves into the transformative role of mesenchymal stem cells (MSCs) in advancing cardiovascular therapeutics. Beginning with a historical perspective, we trace the development of stem cell research related to cardiovascular diseases, highlighting foundational therapeutic approaches and the evolution of cell-based treatments. Recognizing the inherent challenges of MSC-based cardiovascular therapeutics, which range from understanding the pro-reparative activity of MSCs to tailoring patient-specific treatments, we emphasize the need to refine the pro-regenerative capacity of these cells. Crucially, our focus then shifts to the strategies of the fourth generation of cell-based therapies: leveraging the secretomic prowess of MSCs, particularly the role of extracellular vesicles; integrating biocompatible scaffolds and artificial sheets to amplify MSCs’ potential; adopting three-dimensional ex vivo propagation tailored to specific tissue niches; harnessing the promise of genetic modifications for targeted tissue repair; and institutionalizing good manufacturing practice protocols to ensure therapeutic safety and efficacy. We conclude with reflections on these advancements, envisaging a future landscape redefined by MSCs in cardiovascular regeneration. This review offers both a consolidation of our current understanding and a view toward imminent therapeutic horizons.

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Section: Mechanobiologically Mediated Differentiation Of Stem Cellsmentioning

confidence: 99%

Emerging Strategies in Mesenchymal Stem Cell-Based Cardiovascular Therapeutics

Kumar,

Mishra,

Tran

et al. 2024

Cells

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“…Основным методом, используемым для изучения экспрессии секретома МСК in vitro, является разделение с последующей идентификацией белка с помощью масс-спектрометрии, а также других иммунологических анализов [39]. Определение характеристик СМСК с использованием методов, основанных на антителах, предоставляет к изучению лишь узкий спектр факторов, секретируемых МСК [40]. Глобальные протеомные подходы позволили бы лучше понять потенциальную сложность СМСК с финальной целью получения четкого и определенного профиля для надлежащего использования каждой МСК [40].…”

Section: стандартизация смск как афиunclassified

“…Определение характеристик СМСК с использованием методов, основанных на антителах, предоставляет к изучению лишь узкий спектр факторов, секретируемых МСК [40]. Глобальные протеомные подходы позволили бы лучше понять потенциальную сложность СМСК с финальной целью получения четкого и определенного профиля для надлежащего использования каждой МСК [40].…”

Section: стандартизация смск как афиunclassified

Modern aspects of external application and prospects of using the secretome of mesenchymal stem cells (review)

Bakhrushina,

Gravel,

Filippova

et al. 2024

Razrabotka i registraciâ lekarstvennyh sredstv

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Introduction. The secretome of mesenchymal stem cells (SMSC) is widely used in medicine. It is most often used due to its immune-modulating and regenerative properties in the treatment of autoimmune, immuno-mediated and other diseases due to its anti-inflammatory, neuroprotective and regenerating action. In many studies, exosomes isolated from SMSC are used as a therapeutic agent. In recent years, the interest in the development of products containing SMSC for external use has increased. Similar drugs are planned to be used in the treatment of diabetic wounds, for skin regeneration, the treatment of inflammatory diseases, as well as alopecia. There are multiple studies on increasing collagen secretion and reducing skin photosensitivity in preclinical studies, which confirms the significant potential for the use of SMSC in dermatology and cosmetology. The purpose of this review was to study the potential of using conditioned medium in medicines for external use, approaches to standardization of SMSC as a pharmaceutical substance and methods of increasing percutaneous delivery.Text. SMSC as an active pharmaceutical ingredient is a transparent liquid from yellow to orange in color with a characteristic odor. The pH of the ready-to-use SMSC composition ranges from 7.0 to 7.5, which allows it to be used in topical and external applications without the addition of stabilizers or pH correctors. Problems of delivery of SMSC through the epidermis are most often solved by placing the secretome in hydrogels, using exosomes or technology using microneedles. Since 2022, after legislative changes, measures have been taken to register and introduce into clinical practice domestic drugs based on cellular products. However, as the analysis showed, it will take some time before the appearance of original medicines based on SMSC, and today in the Russian Federation only products related to cosmetics and veterinary drugs, as well as zoocosmetics, are produced so far.Conclusion. SMSC may also prove to be a safer and more effective substance for the potential treatment of a wide range of acute and chronic diseases. But despite the large number of positive results of using SMSC for wound healing in animals, as well as clinical studies on skin regeneration, there are no studies of its safety and effectiveness, as well as standardization of the production process.

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“…), получившего название «секретом» [4,5]. Изучению эффективности терапии с использованием пептидов, выделенных из разных тканей, уделяется большое внимание как в зарубежных центрах [6], так и в России [7,8]. Разработан целый ряд подобных препаратов.…”

Section: Introductionunclassified

Comparative characteristics of the effectiveness of preventing the progression of CRF using therapy with secretome of embryonic cell and transplantation of neonatal tissues.

V.I.,

A.V.,

S.A.

et al. 2024

ECU

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Introduction. Literature data and our own research indicate that therapy with immature cell secretion products (secretome) has a pronounced nephroprotective effect both in acute kidney injury and in chronic renal failure (CRF). Considering that the source of the complex of signaling molecules stimulating reparative processes in organs are low-differentiated cells of functionally and anatomically immature organs in a state of deveopment, the question arises to what extent tissue transplantation of these organs reproduces the effect of therapy with a secretome of stem cells in relation to the progression of CRF. Material and methods. The experiments were carried out on 40 outbred male rats weighing 260-290 g, in which CRF was modeled by resection of 4/5 functionally active renal parenchyma. In the 1st series (control), no therapeutic actions were performed. In the 2nd series, after modeling CRF, a course of therapy with Cellex, the active component of which is the secretome of pig embryonic brain cells, was carried out in the form of 2 10-day courses with a 10-day break between them. In the 3rd and 4th series, immediately after CRF modeling, kidney or testicle tissue obtained from newborn baby rats (1-2 days after birth) was injected under the capsule of the resected kidney as a source of immature cells. Tissues of different organs were used to assess the severity of the tissue-specific effect of therapy. Results. 7 days after the modeling of CRF in all series, a deterioration of more than 2 times of all functional parameters was revealed. After 1 month, in the control and in the 2nd and 3rd series, a tendency to an increase in GFR was revealed, which did not reach statistical significance, whereas in the 4th series, the increase in GFR turned out to be statistically significant. After 2 months in the control series, there was a repeated decrease in the GFR index, whereas in all experimental series, GFR continued to increase or remained at subnormal values. The activity of tubular reabsorption of sodium and calcium after a significant decrease after 7 days to 1 month in the control series increased slightly (but unreliably), and after 2 months they again decreased to values 2 times lower than normal. In all experimental series, after 1 and 2 months, the reabsorption of these electrolytes was at values close to normal. The improvement was especially pronounced in groups 2 and 4. After 7 days, the activity of intracellular enzymes (aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH)) in the blood increased in all series with a gradual decrease in hyperfermentemia after 2 months, more pronounced in group 4, as well as in all experimental groups with respect to LDH. Histological examination of the condition of neonatal transplants revealed the destruction of transplanted kidney tissue and a viable testicular graft. Conclusion. Transplantation of neonatal organ tissue under a kidney capsule to rats with CRF has a comparable nephroprotective effect with therapy with the secretome of embryonic cells (Cellex drug). A more pronounced improvement in functional parameters during testicular tissue transplantation is explained by the preservation of the viability of the graft.

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

Cited by 16 publications

References 123 publications

Emerging Strategies in Mesenchymal Stem Cell-Based Cardiovascular Therapeutics

Emerging Strategies in Mesenchymal Stem Cell-Based Cardiovascular Therapeutics

Modern aspects of external application and prospects of using the secretome of mesenchymal stem cells (review)

Comparative characteristics of the effectiveness of preventing the progression of CRF using therapy with secretome of embryonic cell and transplantation of neonatal tissues.

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