Abstract
Human adult stem cell research is a highly prolific area in modern tissue engineering as these cells have significant potential to provide future cellular therapies for the world’s increasingly aged population. Cellular therapies require a smart biomaterial to deliver and localise the cell population; protecting and guiding the stem cells toward predetermined lineage-specific pathways. The cells, in turn, can provide protection to biomaterials and increase its longevity. The right combination of stem cells and biomaterials can significantly increase the therapeutic efficacy. Adult stem cells are utilised to target many changes that negatively impact tissue functions with age. Understanding the underlying mechanisms that lead to changes brought about by the ageing process is imperative as ageing leads to many detrimental effects on stem cell activation, maintenance and differentiation. The circadian clock is an evolutionarily conserved timing mechanism that coordinates physiology, metabolism and behavior with the 24 h solar day to provide temporal tissue homeostasis with the external environment. Circadian rhythms deteriorate with age at both the behavioural and molecular levels, leading to age-associated changes in downstream rhythmic tissue physiology in humans and rodent models. In this review, we highlight recent advances in our knowledge of the role of circadian clocks in adult stem cell maintenance, driven by both cell-autonomous and tissue-specific factors, and the mechanisms by which they co-opt various cellular signaling pathways to impose temporal control on stem cell function. Future research investigating pharmacological and lifestyle interventions by which circadian rhythms within adult stem niches can be manipulated will provide avenues for temporally guided cellular therapies and smart biomaterials to ameliorate age-related tissue deterioration and reduce the burden of chronic disease.
Highlights
Human adult stem cell research is a highly prolific area in modern tissue engineering as these cells have significant potential to provide future cellular therapies for the world’s increasingly aged population
Pioneering experiments in stem cell research are often credited to Canadian scientists Till and McCulloch in 1961–1963, who were the first to carry out clonal colony formation assays on hematopoietic stem cells (HSCs) in murine bone marrow, indicating their multipotency (Becker et al 1963)
They tend to be classified based on their tissue of origin and differentiation potential, and one should perhaps increasingly replace the use of the term adult ‘stem cells’ in favour of adult ‘progenitor cells’
Summary
Pioneering experiments in stem cell research are often credited to Canadian scientists Till and McCulloch in 1961–1963, who were the first to carry out clonal colony formation assays on hematopoietic stem cells (HSCs) in murine bone marrow, indicating their multipotency (Becker et al 1963). Research carried out by Moerman et al (2004) showed that bone marrow aspirates of old mice gave rise to fewer osteoblastic colonies and more adipocytic colonies, when compared to adult mice They concluded that ageing alters the differentiation potential of MSCs, leading to cells being more likely adipogenic than osteogenic. The authors reported that differentiated adipocytes were more readily responsive to clock synchronisation than undifferentiated pre-adipocyte precursors, but the period of clock gene oscillations were longer in differentiated adipocytes, validating the use of ADSCs as in in vitro adult stem cell model for the analysis of circadian rhythms (Wu et al 2007).
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