AGE-RELATED INCREASE IN KYNURENINE LINKED TO DECREASED OSTEOGENESIS VIA REDUCED SDF-1 IN MESENCHYMAL STEM CELLS

AbstractWound healing is a complex process, and disturbance of even a single mechanism can result in chronic ulcers developing after exposure to the alkylating agent sulfur mustard (SM). A possible contributor may be SM-induced chronic senescent mesenchymal stem cells (MSCs), unable to fulfil their regenerative role, by persisting over long time periods and creating a proinflammatory microenvironment. Here we show that senescence induction in human bone marrow derived MSCs was time- and concentration-dependent, and chronic senescence could be verified 3 weeks after exposure to between 10 and 40 µM SM. Morphological changes, reduced clonogenic and migration potential, longer scratch closure times, differences in senescence, motility and DNA damage response associated genes as well as increased levels of proinflammatory cytokines were revealed. Selective removal of these cells by senolytic drugs, in which ABT-263 showed initial potential in vitro, opens the possibility for an innovative treatment strategy for chronic wounds, but also tumors and age-related diseases.

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Mesenchymal Stem Cells Targeting of Systemic Disorders in Age-related Macular Degeneration

Current Tissue Engineering ◽

10.2174/2211542004666150714155725 ◽

2016 ◽

Vol 5 (1) ◽

pp. 60-70 ◽

Cited By ~ 1

Author(s):

Jian Xiong Wang ◽

Marten Erik Brelén ◽

Tsz Kin Ng

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Macular Degeneration ◽

Age Related Macular Degeneration ◽

Age Related

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Mechanisms Underlying the Osteo- and Adipo-Differentiation of Human Mesenchymal Stem Cells

The Scientific World JOURNAL ◽

10.1100/2012/793823 ◽

2012 ◽

Vol 2012 ◽

pp. 1-14 ◽

Cited By ~ 58

Author(s):

Yu Zhang ◽

Dilaware Khan ◽

Julia Delling ◽

Edda Tobiasch

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adipogenic Differentiation ◽

Human Mesenchymal Stem Cells ◽

Human Mscs ◽

Industrialized Countries ◽

Tight Control ◽

Age Related ◽

Donor Cells ◽

Immunosuppressive Microenvironment

Human mesenchymal stem cells (hMSCs) are considered a promising cell source for regenerative medicine, because they have the potential to differentiate into a variety of lineages among which the mesoderm-derived lineages such adipo- or osteogenesis are investigated best. Human MSCs can be harvested in reasonable to large amounts from several parts of the patient’s body and due to this possible autologous origin, allorecognition can be avoided. In addition, even in allogenic origin-derived donor cells, hMSCs generate a local immunosuppressive microenvironment, causing only a weak immune reaction. There is an increasing need for bone replacement in patients from all ages, due to a variety of reasons such as a new recreational behavior in young adults or age-related diseases. Adipogenic differentiation is another interesting lineage, because fat tissue is considered to be a major factor triggering atherosclerosis that ultimately leads to cardiovascular diseases, the main cause of death in industrialized countries. However, understanding the differentiation process in detail is obligatory to achieve a tight control of the process for future clinical applications to avoid undesired side effects. In this review, the current findings for adipo- and osteo-differentiation are summarized together with a brief statement on first clinical trials.

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Age-related intrinsic changes in human bone-marrow-derived mesenchymal stem cells and their differentiation to osteoblasts

Aging Cell ◽

10.1111/j.1474-9726.2008.00377.x ◽

2008 ◽

Vol 7 (3) ◽

pp. 335-343 ◽

Cited By ~ 442

Author(s):

Shuanhu Zhou ◽

Joel S. Greenberger ◽

Michael W. Epperly ◽

Julie P. Goff ◽

Carolyn Adler ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Human Bone ◽

Human Bone Marrow ◽

Age Related

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The Influence of Aging on the Regenerative Potential of Human Adipose Derived Mesenchymal Stem Cells

Stem Cells International ◽

10.1155/2016/2152435 ◽

2016 ◽

Vol 2016 ◽

pp. 1-15 ◽

Cited By ~ 99

Author(s):

Monika Marędziak ◽

Krzysztof Marycz ◽

Krzysztof A. Tomaszewski ◽

Katarzyna Kornicka ◽

Brandon Michael Henry

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adipogenic Differentiation ◽

Population Doubling ◽

Osteogenic Potential ◽

Population Doubling Time ◽

Joint Diseases ◽

Differentiation Potential ◽

Age Related

Tissue regeneration using human adipose derived mesenchymal stem cells (hASCs) has significant potential as a novel treatment for many degenerative bone and joint diseases. Previous studies have established that age negatively affects the proliferation status and the osteogenic and chondrogenic differentiation potential of mesenchymal stem cells. The aim of this study was to assess the age-related maintenance of physiological function and differentiation potential of hASCs in vitro. hASCs were isolated from patients of four different age groups: (1) >20 years (n=7), (2) >50 years (n=7), (3) >60 years (n=7), and (4) >70 years (n=7). The hASCs were characterized according to the number of fibroblasts colony forming unit (CFU-F), proliferation rate, population doubling time (PDT), and quantified parameters of adipogenic, chondrogenic, and osteogenic differentiation. Compared to younger cells, aged hASCs had decreased proliferation rates, decreased chondrogenic and osteogenic potential, and increased senescent features. A shift in favor of adipogenic differentiation with increased age was also observed. As many bone and joint diseases increase in prevalence with age, it is important to consider the negative influence of age on hASCs viability, proliferation status, and multilineage differentiation potential when considering the potential therapeutic applications of hASCs.

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