Enhancement of individual differences in proliferation and differentiation potentials of aged human adipose-derived stem cells

Kawagishi‐Hotta, Mika; Hasegawa, Seiji; Igarashi, Toshio; Yamada, Takaaki; Takahashi, Masuhiro; Numata, Shigeki; Kobayashi, Tatsuhiko; Iwata, Y.; Arima, Masaru; Yamamoto, Naoki; Yagami, Akiko; Nakata, Satoshi; Uzawa, Tohru; Matsunaga, Kayoko; Sugiura, Kazumitsu; Akamatsu, Hirohiko

doi:10.1016/j.reth.2016.12.004

Cited by 33 publications

(33 citation statements)

References 52 publications

(55 reference statements)

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“…After 5 passages of culture, hASCs retained the trilineage differentiation ability. Our results are consistent with the results of Kawagishi-Hotta et al (2016) Kawagishi-Hotta et al (2017. Specifically, when cultured in osteogenic induction medium, the cells were mineralized with the expression of alkaline phosphatase Golub and Boesze-Battaglia (2007), osteocalcin secretion, and calcium phosphate deposition Lee et al (2013).…”

Section: Discussionsupporting

confidence: 93%

Phenotypic and cytogenetic characterization of expanded adipose derived stem cells

Truong

Pham

2018

Sci. Tech. Dev. J.

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Introduction: Human adipose derived stem cells (hASCs) have great potential for regenerative medicine. The demand for hASCs, especially in the development of off-the-shelf products, is increasing. Although the initial receipt of hASCs was relatively limited, there is now greater interest and also awareness that in vitro expansion of hASCs be further explored. The purpose of this study was to assess the integrity of mesenchymal cell characteristics and the mutant capability of chromosome number on hASCs undergoing in vitro expansion. Methods: In this study, three hASC samples from three Vietnamese people were collected and proliferated in MSCCult medium (Regemedlab, Ho Chi Minh City, Viet Nam) to the 5th cell passage. Next, hASCs were evaluated for change of mesenchymal stem cells (MSCs) characteristics including shape, immunophenotype (CD14, CD34, CD44, CD73, CD90, and/or CD166), and trilineage differentiation ability. Finally, the number of chromosomes after passages 1, 3, and 5 was evaluated by karyotyping technique. Results: The results showed that after five passages of culture, hASCs preserved the characteristic shape of MSCs, high expression of mesenchymal markers (e.g. CD44, CD73, CD90, and CD166). However, the cells also maintained their differentiation capacity to develop into various tissues such as bone, cartilage, and fat. The hASCs showed no mutation in the number of chromosomes. However, markers of hematopoietic cells (such as CD14 and CD34) exhibited heterogeneous changes between the samples during proliferation. Conclusion: In conclusion, at passage 5, hASCs retained the integrity of MSC features and there was no mutation discovered in the number of chromosomes. However, further evaluation is needed to conclude that the use of cultured cells in treatment is effective and safe.

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Section: Discussionsupporting

confidence: 93%

Phenotypic and cytogenetic characterization of expanded adipose derived stem cells

Truong

Pham

2018

Sci. Tech. Dev. J.

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“…Commercial SVF preparation systems have previously highlighted the necessity for in-depth analysis of safety profiling, viable cell analysis, and ultimately clinical trials in order to understand and finely tune the action and benefit [27]. The “quality” of fractions and their MSC content may indeed vary from patient to patient [28]; however, so far, when used in various treatment regimens, these differences have not been shown to significantly alter the outcome [29]. SVF or their purified MSC content has been reported in the literature to have potential therapeutic value [30], but a full characterization of component vs. effect is still lacking.…”

Section: Discussionmentioning

confidence: 99%

Long-Lasting Anti-Inflammatory Activity of Human Microfragmented Adipose Tissue

Nava

Sordi

Pascucci

et al. 2019

Stem Cells International

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Over the last few years, human microfragmented adipose tissue (MFAT), containing significant levels of mesenchymal stromal cells (MSCs) and obtained from fat lipoaspirate (LP) through a minimal manipulation in a closed system device, has been successfully used in aesthetic medicine as well as in orthopedic and general surgery. Interestingly, in orthopedic diseases, this ready-to-use adipose tissue cell derivative seems to have a prolonged time efficacy even upon a single shot injection into osteoarthritic tissues. Here, we investigated the long-term survival and content of MSCs as well the anti-inflammatory activity of LP and its derived MFAT in vitro, with the aim to better understand a possible in vivo mechanism of action. MFAT and LP specimens from 17 human donors were investigated side by side. During a long-term culture in serum-free medium, we found that the total cell number as well the MSC content in MFAT decreased more slowly if compared to those from LP specimens. The analysis of cytokines and growth factors secreted into the conditioned medium (CM) was similar in MFAT and LP during the first week of culture, but the total amount of cytokines secreted by LP decreased much more rapidly than those produced by MFAT during prolonged culture (up to 28 days). Similarly, the addition of MFAT-CM recovered at early (3-7 days) and late stage (14-28 days) of culture strongly inhibited inflammatory function of U937 monocyte cell line, whereas the anti-inflammatory activity of LP-CM was drastically reduced after only 7 days of culture. We conclude that MFAT is an effective preparation with a long-lasting anti-inflammatory activity probably mediated by a long-term survival of their MSC content that releases a combination of cytokines that affect several mechanisms involved in inflammation processes.

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“…In the present study, we have investigated aging-associated Cdc42 activity in adiposederived MSCs isolated from male rats of different ages and tested the effects of pharmacological inhibition of Cdc42 in MSCs isolated from aged animals. We focused on males in order to exclude gender effects since there is accumulating evidence that age-related alterations of mesenchymal stem cells can be modulated by sex hormones and estrogen decreases Cdc42 activity (Azios et al 2007;Breu et al 2011;Fossett et al 2012;Kawagishi-Hotta et al 2017).…”

Section: Discussionmentioning

confidence: 99%

Elevated levels of the small GTPase Cdc42 induces senescence in male rat mesenchymal stem cells

et al. 2018

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Mesenchymal stem cells (MSCs) represent a promising cell source for cellular therapy and tissue engineering and are currently being tested in a number of clinical trials for various diseases. However, like other somatic cells, MSCs age, and this senescence is accompanied by a progressive decline in stem cell function. Several lines of evidence suggest a role for the Rho family GTPase Cdc42 activity in cellular senescence processes. In the present study, we have examined aging-associated Cdc42 activity in rat adipose-derived mesenchymal stem cells (ADMSCs) and the consequences of pharmacological inhibition of Cdc42 in ADMSCs from aged rats. We demonstrate that ADMSCs show a decreased rate of cell growth and a decreased ability to differentiate into chrodrogenic, osteogenic and adipogenic cell lineages as a function of rat age. This is accompanied with an increased staining for SA-β-Gal activity and increased levels of Cdc42 bound to GTP. Treatment of ADMSCs from 24-month old rats with three Cdc42 inhibitors significantly increased proliferation rates, decreased SA-β-Gal staining, and reduced Cdc42-GTP. The Cdc42 inhibitor CASIN increased adipogenic and osteogenic differentiation potential in ADMSCs from 24-month old rats, and decreased the levels of radical oxygen species (ROS), p16 levels, F-actin, and the activity of the ERK1/2 and JNK signaling pathways that were all elevated in these cells. These data suggest that ADMSCs show increased rates of senescence as rats age that appear to be due to elevated Cdc42 activity. Thus, Cdc42 plays important roles in MSC senescence and differentiation potential, and pharmacological reduction of Cdc42 activity can, at least partially, rejuvenate aged MSCs.

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Enhancement of individual differences in proliferation and differentiation potentials of aged human adipose-derived stem cells

Cited by 33 publications

References 52 publications

Phenotypic and cytogenetic characterization of expanded adipose derived stem cells

Phenotypic and cytogenetic characterization of expanded adipose derived stem cells

Long-Lasting Anti-Inflammatory Activity of Human Microfragmented Adipose Tissue

Elevated levels of the small GTPase Cdc42 induces senescence in male rat mesenchymal stem cells

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