Human adipose-derived mesenchymal stromal cells from face and abdomen undergo replicative senescence and loss of genetic integrity after long-term culture

Delben, Priscilla Barros; Zomer, Helena Debiazi; Silva, Camila Acordi da; Gomes, Rogério; Melo, Fernanda Rosene; Dillenburg-Pilla, Patrícia; Trentin, Andréa Gonçalves

doi:10.1016/j.yexcr.2021.112740

Cited by 6 publications

(5 citation statements)

References 65 publications

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“…Mesenchymal stem/stromal cells (MSCs) are multipotent stem cells present in virtually all adult tissues that participate in homeostasis and repair by the secretion of paracrine factors and differentiation in tissue-specific cells [ 1 – 4 ]. MSCs can be isolated with high yield and maintain their proliferative capacity and genetic stability for several passages in vitro [ 5 – 7 ]. They are classified as low or non-immunogenic as they express low levels of MHC I and lack MHC II and other co-stimulatory molecules.…”

Section: Introductionmentioning

confidence: 99%

“…We have previously isolated and characterized MSCs derived from the human dermis and adipose tissue (DSCs and ASCs, respectively) harvested from tissues discarded after elective abdominoplasties [ 5 , 7 , 20 ]. We have shown that both DSCs and ASCs share the general MSC immunophenotype (CD73+, CD90+, CD105+, CD34−, and CD45−) and mesodermal differentiation potential (adipogenic, osteogenic, and chondrogenic).…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of secretomes derived from human dermal and adipose tissue mesenchymal stem/stromal cells for skin wound healing: not as effective as cells

Zomer,

de Souza Lima,

Bion

et al. 2024

Stem Cell Res Ther

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Background Although the paracrine effects of mesenchymal stem/stromal cells (MSCs) have been recognized as crucial mediators of their regenerative effects on tissue repair, the potential of MSC secretomes as effective substitutes for cellular therapies remains underexplored. Methods In this study, we compared MSCs from the human dermis (DSCs) and adipose tissue (ASCs) with their secretomes regarding their efficacy for skin wound healing using a translationally relevant murine model. Results Proteomic analysis revealed that while there was a substantial overlap in protein composition between DSC and ASC secretomes, specific proteins associated with wound healing and angiogenesis were differentially expressed. Despite a similar angiogenic potential in vivo, DSC and ASC secretomes were found to be less effective than cells in accelerating wound closure and promoting tissue remodeling. Conclusions Overall, secretome-treated groups showed intermediary results between cells- and control-treated (empty scaffold) groups. These findings highlight that although secretomes possess therapeutic potential, their efficacy might be limited compared to cellular therapies. This study contributes to the growing understanding of MSC secretomes, emphasizes the need for further protocol optimization, and offers insights into their potential applications in regenerative medicine.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Evaluation of secretomes derived from human dermal and adipose tissue mesenchymal stem/stromal cells for skin wound healing: not as effective as cells

Zomer,

de Souza Lima,

Bion

et al. 2024

Stem Cell Res Ther

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“…Our single monocyte cultures had a senescent appearance after the second week, much like the same monocytes cocultured with MSCs for 4 weeks. Interestingly, MSCs withstand many doublings and, therefore, a long time in culture without changing their appearance or phenotype (but under defined optimal culture conditions) [58]. The two cell types in coculture maintained their typical characteristics longer, demonstrating the existence of nourishing and cooperative behavior between them.…”

Section: Discussionmentioning

confidence: 99%

Cytokine Profile and Anti-Inflammatory Activity of a Standardized Conditioned Medium Obtained by Coculture of Monocytes and Mesenchymal Stromal Cells (PRS CK STORM)

et al. 2022

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Intercellular communication between monocytes/macrophages and cells involved in tissue regeneration, such as mesenchymal stromal cells (MSCs) and primary tissue cells, is essential for tissue regeneration and recovery of homeostasis. Typically, in the final phase of the inflammation-resolving process, this intercellular communication drives an anti-inflammatory immunomodulatory response. To obtain a safe and effective treatment to counteract the cytokine storm associated with a disproportionate immune response to severe infections, including that associated with COVID-19, by means of naturally balanced immunomodulation, our group has standardized the production under GMP-like conditions of a secretome by coculture of macrophages and MSCs. To characterize this proteome, we determined the expression of molecules related to cellular immune response and tissue regeneration, as well as its possible toxicity and anti-inflammatory potency. The results show a specific molecular pattern of interaction between the two cell types studied, with an anti-inflammatory and regenerative profile. In addition, the secretome is not toxic by itself on human PBMC or on THP-1 monocytes and prevents lipopolysaccharide (LPS)-induced growth effects on those cell types. Finally, PRS CK STORM prevents LPS-induced TNF-A and IL-1Β secretion from PBMC and from THP-1 cells at the same level as hydrocortisone, demonstrating its anti-inflammatory potency.

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“…Strikingly, a recent study reported that rodent MSCs secrete E2 in vitro and in vivo and suggested that E2 secretion by MSCs is responsible for their therapeutic potential (Li et al, 2015). However, endogenous E2 levels were shown to interfere with MSC activity and cells isolated from aged or estrogen-deficient individuals showed impaired functions (Yao et al, 2016;Zhuge et al, 2018;Delben et al, 2021;Elliot et al, 2022). The complex crosstalk between E2 and MSCs needs to be further investigated.…”

Section: Regenerative Medicine Approachesmentioning

confidence: 99%

Targeting estrogen signaling and biosynthesis for aged skin repair

Zomer,

Cooke

2023

Front. Physiol.

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Non-healing skin wounds are disproportionally prevalent in older adults. Current treatments do not account for the particularities of aged skin and result in inadequate outcomes. Overall, healing chronic wounds in the elderly remains a major unmet clinical need. Estrogens play a critical role in reproduction but also have important actions in non-reproductive organs. Estrogen biosynthesis and signaling pathways are locally activated during physiological wound healing, processes that are inhibited in elderly estrogen-deprived skin. Estrogen deprivation has been shown to be a critical mediator of impaired wound healing in both postmenopausal women and aged men, and topical estrogen application reverses age-associated delayed wound healing in both elderly men and women. These data indicate that adequate estrogen biosynthesis and properly regulated estrogen signaling pathways are essential for normal wound healing and can be targeted to optimize tissue repair in the elderly. However, due to fundamental questions regarding how to safely restore estrogen signaling locally in skin wounds, there are currently no therapeutic strategies addressing estrogen deficiency in elderly chronic wounds. This review discusses established and recent literature in this area and proposes the hypothesis that estrogen plays a pleiotropic role in skin aging and that targeting estrogen signaling and biosynthesis could promote skin repair in older adults.

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Human adipose-derived mesenchymal stromal cells from face and abdomen undergo replicative senescence and loss of genetic integrity after long-term culture

Cited by 6 publications

References 65 publications

Evaluation of secretomes derived from human dermal and adipose tissue mesenchymal stem/stromal cells for skin wound healing: not as effective as cells

Evaluation of secretomes derived from human dermal and adipose tissue mesenchymal stem/stromal cells for skin wound healing: not as effective as cells

Cytokine Profile and Anti-Inflammatory Activity of a Standardized Conditioned Medium Obtained by Coculture of Monocytes and Mesenchymal Stromal Cells (PRS CK STORM)

Targeting estrogen signaling and biosynthesis for aged skin repair

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