The biology of telomeres in multipotential stromal cells

Dimitrios Kouroupis, Sarah M. Churchman, Elena A. Jones

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Multipotential stromal cells, also known as mesenchymal stem cells (MSCs), reside within the bone marrow (BM) and other skeletal and connective tissues. They serve as a reserve of progenitors for continuous cell replacement during normal tissue homeostasis. Furthermore, MSCs are responsible for production of replacement cells lost as a result of acute or chronic injury to bone, cartilage, tendon, meniscus and other connective tissues and are involved in physiological bone remodeling. Loss of MSC function is apparent in the older individual, potentially contributing to the development of osteoporosis and osteoarthritis; dyskeratosis and Werner's syndromes are also linked to premature aging of skeletal and connective tissues. Telomere attrition has been proposed as a possible mechanism for the loss of MSC function, and may represent a therapeutic target in these diseases. MSCs can be culture-expanded with relative ease and are already used therapeutically to repair cartilage and bone defects following injury. Also, because of their well-described immunoregulatory capacity, MSC therapy is used to treat patients with graft-versus-host disease. It is therefore very important to monitor telomere dynamics during MSC manufacture, for the purpose of controlling their therapeutic potency and potential for spontaneous transformation. We will outline the current understanding of MSC ageing in vitro and observed telomere loss during culture expansion, primarily focusing on MSCs derived from adult tissues (BM, adipose and dental pulp), but also discussing perinatal tissues such as umbilical cord. Various telomere length measurement methods will be described and compared, in terms of their utility and practicality. Safety concerns relating to genetic manipulation of MSCs to extend their proliferation span, and the subsequent quantity of manufactured MSCs will be discussed. Finally, we evaluate in vivo MSC ageing compared to that of hematopoietic stem cells highlighting both similarities and differences, which in our view stems from the current lack of robust methods for native MSC isolation directly from skeletal tissues. This combined knowledge should undoubtedly advance our understanding of MSC function during ageing and is likely to contribute to the development of novel therapies for age-related skeletal diseases.

Original languageEnglish (US)
Title of host publicationAdvances in Genetics Research
PublisherNova Science Publishers, Inc.
Pages53-78
Number of pages26
Volume12
ISBN (Electronic)9781633213524
ISBN (Print)9781633213517
StatePublished - Jul 1 2014
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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