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), residewithin the bone marrow (BM) and other skeletal and connective tissues. They serve as areserve of progenitors for continuous cell replacement during normal tissue homeostasis.Furthermore, MSCs are responsible for production of replacement cells lost as a result ofacute or chronic injury to bone, cartilage, tendon, meniscus and other connective tissuesand are involved in physiological bone remodeling. Loss of MSC function is apparent inthe older individual, potentially contributing to the development of osteoporosis andosteoarthritis; dyskeratosis and Werner's syndromes are also linked to premature aging ofskeletal and connective tissues. Telomere attrition has been proposed as a possiblemechanism for the loss of MSC function, and may represent a therapeutic target in thesediseases.MSCs can be culture-expanded with relative ease and are already usedtherapeutically to repair cartilage and bone defects following injury. Also, because oftheir well-described immunoregulatory capacity, MSC therapy is used to treat patientswith graft-versus-host disease. It is therefore very important to monitor telomeredynamics during MSC manufacture, for the purpose of controlling their therapeuticpotency and potential for spontaneous transformation.We will outline the current understanding of MSC ageing in vitro and observedtelomere loss during culture expansion, primarily focusing on MSCs derived from adulttissues (BM, adipose and dental pulp), but also discussing perinatal tissues such asumbilical cord. Various telomere length measurement methods will be described andcompared, in terms of their utility and practicality. Safety concerns relating to geneticmanipulation of MSCs to extend their proliferation span, and the subsequent quantity ofmanufactured MSCs will be discussed. Finally, we evaluate in vivo MSC ageing compared to that of hematopoietic stemcells highlighting both similarities and differences, which in our view stems from thecurrent lack of robust methods for native MSC isolation directly from skeletal tissues.This combined knowledge should undoubtedly advance our understanding of MSCfunction during ageing and is likely to contribute to the development of novel therapiesfor age-related skeletal diseases.

Original languageEnglish (US)
Title of host publicationTelomeres
Subtitle of host publicationBiological Functions, Sequencing and Aging
PublisherNova Science Publishers, Inc.
Pages1-26
Number of pages26
ISBN (Print)9781619426344
StatePublished - Sep 2012
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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