Influence of aging on the quantity and quality of human cardiac stem cells

Nakamura, Tamami; Hosoyama, Tohru; Kawamura, Daichi; Takeuchi, Yuriko; Tanaka, Yuya; Samura, Makoto; Ueno, Koji; Nishimoto, Arata; Kurazumi, Hiroshi; Suzuki, Ryo; Ito, Hiroshi; Sakata, Kensuke; Mikamo, Akihito; Li, Tao‐Sheng; Hamano, Kimikazu

doi:10.1038/srep22781

Cited by 23 publications

(19 citation statements)

References 42 publications

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“…A recent study showed that human Isl1 pos c-kit pos CPC isolated from adult patients harbor an altered miRNA expression profile that correlated with a reduced proliferation capacity and abrogated response to growth factors compared to Isl1 pos c-kit pos CPC derived from neonates 22 . Another study, comparing CDCs derived from patients of various ages, showed limited differences in proliferation capacity, angiogenic potential and expression of growth factors between CDCs from young and elderly patients (≥65 years) 23 . However, in this study the youngest donor was 2 years old, the median age 72.5 years and 61.5% of them were 65 years or older which is in striking contrast with our study.…”

Section: Discussionmentioning

confidence: 99%

Molecular signature of progenitor cells isolated from young and adult human hearts

Walravens

Vanhaverbeke

Ottaviani

et al. 2018

Sci Rep

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The loss of endogenous cardiac regenerative capacity within the first week of postnatal life has intensified clinical trials to induce cardiac regeneration in the adult mammalian heart using different progenitor cell types. We hypothesized that donor age-related phenotypic and functional characteristics of cardiac progenitor cells (CPC) account for mixed results of cell-based cardiac repair. We compared expression profiles and cell turnover rates of human heart-derived c-kitpos progenitors (c-kitpos CPC) and cardiosphere-derived cells (CDC) from young and adult donor origin and studied their in vitro angiogenic and cardiac differentiation potential, which can be relevant for cardiac repair. We report that 3-dimensional CDC expansion recapitulates a conducive environment for growth factor and cytokine release from adult donor cells (aCDC) that optimally supports vascular tube formation and vessel sprouting. Transdifferentiation capacity of c-kitpos CPCs and CDCs towards cardiomyocyte-like cells was modest, however, most notable in young c-kitpos cells and adult CDCs. Progenitors isolated with different methods thus show cell- and donor-specific characteristics that may account for variable contributions in functional myocardial recovery.

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Section: Discussionmentioning

confidence: 99%

Molecular signature of progenitor cells isolated from young and adult human hearts

Walravens

Vanhaverbeke

Ottaviani

et al. 2018

Sci Rep

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“…Although autologous stem cell transplantation holds some advantages, including safety of approach and reduction of virus or disease transmission; it also has disadvantages, namely the uncertainty of stem cell quality. Several studies have shown stem cell quality significantly decreases in older patients, and under certain conditions (Beane et al, 2014;Nakamura et al, 2016). Therefore, allogeneic stem cell therapy is regarded as a considered as suitable alternative to autologous transplantation.…”

Section: Discussionmentioning

confidence: 99%

Umbilical cord-derived stem cells (ModulatistTM) show strong immunomodulation capacity compared to adipose tissue-derived or bone marrow-derived mesenchymal stem cells

Pham¹,

Vu²,

Phan³

2016

Biomed Res Ther

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Abstract-Introduction:Mesenchymal stem cells (MSCs) show great promise in regenerative medicine. Clinical applications of MSCs have recently increased significantly, especially for immune diseases. Autologous transplantation is considered a safe therapy. However, its main disadvantages are poor stability and quality of MSCs from patient to patient, and labor-intensive and time-consuming culture procedures. Therefore, allogeneic MSC transplantation has recently emerged as a potential replacement for autologous transplantation. "Off the shelf" MSC products, or socalled "stem cell drugs", have rapidly developed; these products have already been approved in various countries, including Canada, Korea and Japan. This study aims to evaluate a new stem cell product or "drug", termed Modulatist TM , derived from umbilical cord mesenchymal stem cells (UCMSCs), which have strong immunomodulatory properties, compared to bone marrow-derived MSCs (BMMSCs) or adipose tissue-derived stem cells (ADSCs). Methods: Modulatist TM was produced from MSCs derived from whole umbilical cord (UC) tissue (which includes Wharton's jelly and UC), according to GMP compliant procedures. Bone marrow-and adipose tissue-derived MSCs were isolated and proliferated in standard conditions, according to GMP compliant procedures. Immunomodulation mediated by MSCs was assessed by allogenic T cell suppression and cytokine release; role of prostaglandin E2 in the immunomodulation was also evaluated. Results: The results showed that Modulatist TM exhibited stronger immunomodulation than BMMSC and ADSC in vitro. Modulatist TM strongly suppressed allogeneic T cells proliferation and decreased cytokine production, compared to BMMSCs and ADSCs. Conclusion: Modulatist TM is a strong immunomodulator and promising MSC product. It may be useful to modulate or treat autoimmune diseases.

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“…[ 7 ] Nakamura et al observed a good correlation with age in the expression of senescence markers in cardiosphere derived cells from aged hearts; but, no correlation was observed between age and growth rate, angiogenic ability and growth factor production. [ 8 ] These preliminary observations in human samples underscore the requirement for a systematic analysis of the variation in stem cell characteristics with age and disease, using an appropriate animal model. Deterioration in stem cell characteristics is possibly mediated by a suboptimal microenvironment.…”

Section: Introductionmentioning

confidence: 98%

Accelerated decline in cardiac stem cell efficiency in Spontaneously hypertensive rat compared to normotensive Wistar rat

Saheera

Nair

2017

PLoS ONE

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Cardiac hypertrophy is recognized as an independent risk factor for cardiac failure. Efficient management of hypertensive heart disease requires identification of factors that can possibly mediate the transition from hypertrophy to failure. Resident cardiac stem cells have a prominent role in the maintenance of cardiac tissue homeostasis. Decline in the proportion of healthy cardiac stem cells (CSCs) can affect tissue regeneration. In pathological conditions, apart from natural aging, an adverse microenvironment can lead to decrease in efficiency of CSCs. A systematic analysis of cardiac stem cell characteristics in pathological conditions has not been reported so far. Therefore, this study was designed with the objective of examining the age associated variation in stem cell attributes of Spontaneously hypertensive rat (SHR) in comparison with normotensive Wistar rat. Spontaneously hypertensive rat was used as the experimental model since the cardiac remodeling resembles the clinical course of hypertensive heart disease. CSCs were isolated from atrial explants. Stem cell attributes were assessed in 1-week, 6, 12 and 18-month-old male SHR, in comparison with age matched Wistar rats. In 1-week-old pups, stem cell attributes of SHR and Wistar were comparable. Migration potential, proliferative capacity, TERT expression, telomerase activity and the proportion of c-kit+ cells decreased with age, both in SHR and Wistar. DNA damage and the proportion of senescent CSCs increased with age both in SHR and Wistar rats. Age associated increase was observed in the oxidative stress of stem cells, possibly mediated by the enhanced oxidative stress in the microenvironment. The changes were more pronounced in SHR, and as early as six months of age, there was significant decrease in efficiency of CSCs of SHR compared to Wistar. The density of healthy CSCs determined as a fraction of the differentiated cells was remarkably low in 18-month-old SHR. Age associated decrease in functionally efficient CSCs was therefore accelerated in SHR. Considering the vital role of CSCs in the maintenance of a healthy myocardium, decrease in functionally efficient CSCs can be a precipitating factor in pathological cardiac remodeling. Elevated ROS levels in CSCs of SHR lends scope for speculation that decrease in efficiency of CSCs is mediated by oxidative stress; and that modulation of the microenvironment by therapeutic interventions can restore a healthy stem cell population and facilitate maintenance of cardiac homeostasis and prevent cardiac decompensation.

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Influence of aging on the quantity and quality of human cardiac stem cells

Cited by 23 publications

References 42 publications

Molecular signature of progenitor cells isolated from young and adult human hearts

Molecular signature of progenitor cells isolated from young and adult human hearts

Umbilical cord-derived stem cells (ModulatistTM) show strong immunomodulation capacity compared to adipose tissue-derived or bone marrow-derived mesenchymal stem cells

Accelerated decline in cardiac stem cell efficiency in Spontaneously hypertensive rat compared to normotensive Wistar rat

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