The Effect of Age on Human Adipose-Derived Stem Cells

Wu, Wei; Niklason, Laura E.; Steinbacher, Derek M.

doi:10.1097/prs.0b013e3182729cfc

Cited by 109 publications

(86 citation statements)

References 35 publications

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“…Results presented in this study and elsewhere suggest that thymus MSCs may be a promising candidate for therapeutic use [6,7]. Given the low expression human leukocyte antigen class I on a subset of neonatal human thymus MSCs, as shown in this study and elsewhere [7,70], use of these MSCs may also yield advantages in the allogeneic setting (e.g., use in older patients with ischemic heart disease), in which it is more likely to complement the advantages of neonatal MSCs over adult MSCs [71][72][73]. However, improvements in isolation yield are needed to make clinical use of thymus MSCs feasible.…”

Section: Discussionmentioning

confidence: 99%

Characterization and Angiogenic Potential of Human Neonatal and Infant Thymus Mesenchymal Stromal Cells

Wang

Mundada

Johnson

et al. 2015

Stem Cells Translational Medicine

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Mesenchymal stromal cells (MSCs) are present in large numbers in discarded neonatal and infant thymus tissue and can be isolated by an explant culture method. Explant culture‐isolated thymus MSCs demonstrate the classical characteristics of bone marrow MSCs. Thymus MSCs also possess proangiogenic qualities and deserve further consideration as a potential cell therapeutic agent to promote tissue regeneration and repair and for use in strategies to vascularize engineered tissues.

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Section: Discussionmentioning

confidence: 99%

Characterization and Angiogenic Potential of Human Neonatal and Infant Thymus Mesenchymal Stromal Cells

Wang

Mundada

Johnson

et al. 2015

Stem Cells Translational Medicine

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“…Whereas bone marrow has been shown to be a source of stem cells, it is particularly important to consider the use of adipose-derived mesenchymal stem cells (AD-MSCs) due to their ease of isolation and abundance. Whereas there have been studies noting various changes in AD-MSC properties with aging [74][75][76]78,79,82,83,85 and diabetes, 71 it is unclear how donor demographics affect functions related to vascular engineering such as the ability to secrete factors to induce SMC migration and their potential to differentiate into SMCs. Also, investigating if donor demographics alter the factors secreted by AD-MSCs will have a broad impact as the AD-MSC secretome has been used for a variety of applications.…”

Section: Introductionmentioning

confidence: 99%

“…While taken together, these studies have shown that cellularizing tissue-engineered grafts significantly improves the patency and regeneration over their acellular counterparts; these models hold limited relevance for clinical translation since in practice, cells would need to be harvested from patients at high cardiovascular risk such as diabetics 64,65 and the elderly. [66][67][68] In addition, these high-risk groups possess pathologic conditions such as a hyperglycemic environment [69][70][71][72] and ageassociated senescence, [73][74][75][76][77][78][79][80][81][82][83][84][85] respectively, which can decrease the ability of their stem cells to proliferate, differentiate into specific mesenchymal cell types, and promote angiogenesis. Whereas bone marrow has been shown to be a source of stem cells, it is particularly important to consider the use of adipose-derived mesenchymal stem cells (AD-MSCs) due to their ease of isolation and abundance.…”

Section: Introductionmentioning

confidence: 99%

A Cautionary Tale for Autologous Vascular Tissue Engineering: Impact of Human Demographics on the Ability of Adipose-Derived Mesenchymal Stem Cells to Recruit and Differentiate into Smooth Muscle Cells

KrawiecJeffrey

Weinbaum²,

M.³

et al. 2015

Tissue Engineering Part A

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Autologous tissue-engineered blood vessels (TEBVs) generated using adult stem cells have shown promising results, but many preclinical evaluations do not test the efficacy of stem cells from patient populations likely to need therapy (i.e., elderly and diabetic humans). Two critical functions of these cells will be (i) secreting factors that induce the migration of host cells into the graft and (ii) differentiating into functional vascular cells themselves. The purpose of this study was to analyze whether adipose-derived mesenchymal stem cells (AD-MSCs) sourced from diabetic and elderly patients have a reduced ability to promote human smooth muscle cell (SMC) migration and differentiation potential toward SMCs, two important processes in stem cell-based tissue engineering of vascular grafts. SMC monolayers were disrupted in vitro by a scratch wound and were induced to close the wound by exposure to media conditioned by AD-MSCs from healthy, elderly, and diabetic patients. Media conditioned by AD-MSCs from healthy patients promoted the migration of SMCs and did so in a dose-dependent manner; heating the media to 56°C eliminated the media's potency. AD-MSCs from diabetic and elderly patients had a decreased ability to differentiate into SMCs under angiotensin II stimulation; however, only AD-MSCs from elderly donors were unable to promote SMC migration. Gender and body-mass index of the patients showed no effect on either critical function of AD-MSCs. In conclusion, AD-MSCs from elderly patients may not be suitable for autologous TEBVs due to inadequate promotion of SMC migration and differentiation.

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“…The inter-subject variability inevitably influences the evaluation of cellular osteogenic potential due to differences in age, physiologic and hormonal state, and health conditions and gender of the donors. 9,10 Therefore, the ideal experimental scenario would assess osteogenic differentiation of MCs obtained from different tissues in the same donor. Then, a direct comparison can be performed to assess ACs and BMCs under the same conditions, with an emphasis on optimized bone formation.…”

Section: Introductionmentioning

confidence: 99%

Osteogenic Performance of Donor-Matched Human Adipose and Bone Marrow Mesenchymal Cells Under Dynamic Culture

Mendez

et al. 2015

Tissue Engineering Part A

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Adipose-derived mesenchymal cells (ACs) and bone marrow-derived mesenchymal cells (BMCs) have been widely used for bone regeneration and can be seeded on a variety of rigid scaffolds. However, to date, a direct comparison of mesenchymal cells (MC) harvested from different tissues from the same donor and cultured in identical osteogenic conditions has not been investigated. Indeed, it is unclear whether marrow-derived or fatderived MC possess intrinsic differences in bone-forming capabilities, since within-patient comparisons have not been previously done. This study aims at comparing ACs and BMCs from three donors ranging in age from neonatal to adult. Matched cells from each donor were studied in three distinct bioreactor settings, to determine the best method to create a viable osseous engineered construct. Human ACs and BMCs were isolated from each donor, cultured, and seeded on decellularized porcine bone (DCB) constructs. The constructs were then subjected to either static or dynamic (stirring or perfusion) bioreactor culture conditions for 7-21 days. Afterward, the constructs were analyzed for cell adhesion and distribution and osteogenic differentiation. ACs demonstrated higher seeding efficiency than BMCs. However, static and dynamic culture significantly increased BMCs proliferation more than ACs. In all conditions, BMCs demonstrated stronger osteogenic activity as compared with ACs, through higher alkaline phosphatase activity and gene expression for various bony markers. Conversely, ACs expressed more collagen I, which is a nonspecific matrix molecule in most connective tissues. Overall, dynamic bioreactor culture conditions enhanced osteogenic gene expression in both ACs and BMCs. Scaffolds seeded with BMCs in dynamic stirring culture conditions exhibit the greatest osteogenic proliferation and function in vitro, proving that marrow-derived MC have superior bone-forming potential as compared with adipose-derived cells.

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The Effect of Age on Human Adipose-Derived Stem Cells

Cited by 109 publications

References 35 publications

Characterization and Angiogenic Potential of Human Neonatal and Infant Thymus Mesenchymal Stromal Cells

Characterization and Angiogenic Potential of Human Neonatal and Infant Thymus Mesenchymal Stromal Cells

A Cautionary Tale for Autologous Vascular Tissue Engineering: Impact of Human Demographics on the Ability of Adipose-Derived Mesenchymal Stem Cells to Recruit and Differentiate into Smooth Muscle Cells

Osteogenic Performance of Donor-Matched Human Adipose and Bone Marrow Mesenchymal Cells Under Dynamic Culture

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