Nanotopography controls cell cycle changes involved with skeletal stem cell self-renewal and multipotency

نویسندگان

  • Louisa C.Y. Lee
  • Nikolaj Gadegaard
  • María C. de Andrés
  • Lesley-Anne Turner
  • Karl V. Burgess
  • Stephen J. Yarwood
  • Julia Wells
  • Manuel Salmeron-Sanchez
  • Dominic Meek
  • Richard O.C. Oreffo
  • Matthew J. Dalby
چکیده

In culture isolated bone marrow mesenchymal stem cells (more precisely termed skeletal stem cells, SSCs) spontaneously differentiate into fibroblasts, preventing the growth of large numbers of multipotent SSCs for use in regenerative medicine. However, the mechanisms that regulate the expansion of SSCs, while maintaining multipotency and preventing fibroblastic differentiation are poorly understood. Major hurdles to understanding how the maintenance of SSCs is regulated are (a) SSCs isolated from bone marrow are heterogeneous populations with different proliferative characteristics and (b) a lack of tools to investigate SSC number expansion and multipotency. Here, a nanotopographical surface is used as a tool that permits SSC proliferation while maintaining multipotency. It is demonstrated that retention of SSC phenotype in culture requires adjustments to the cell cycle that are linked to changes in the activation of the mitogen activated protein kinases. This demonstrates that biomaterials can offer cross-SSC culture tools and that the biological processes that determine whether SSCs retain multipotency or differentiate into fibroblasts are subtle, in terms of biochemical control, but are profound in terms of determining cell fate.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Functional Inhibition of Nucleostemin Gene-Acoordinator of Self-Renewal Ability-In Bone Marrow Derived Mesenchymal Stem Cells by Rnai Strategy

Purpose: The aim is to downregulate the expression level of NS as an important factor in sustaining stem cells and certain types of cancer cells self-renewal ability in bone marrow derived mesenchymal stem cells by RNAi strategy and investigate the effects of absence of NS in these cells. Materials and Methods: Double strand NS-specific and control siRNA oligos were designed and transfected in...

متن کامل

Mechanisms of stem cell self-renewal.

Self-renewal is the process by which stem cells divide to make more stem cells, perpetuating the stem cell pool throughout life. Self-renewal is division with maintenance of the undifferentiated state. This requires cell cycle control and often maintenance of multipotency or pluripotency, depending on the stem cell. Self-renewal programs involve networks that balance proto-oncogenes (promoting ...

متن کامل

Self-Renewal, Multipotency, and the Existence of Two Cell Populations within an Epithelial Stem Cell Niche

In adult skin, each hair follicle contains a reservoir of stem cells (the bulge), which can be mobilized to regenerate the new follicle with each hair cycle and to reepithelialize epidermis during wound repair. Here we report new methods that permit their clonal analyses and engraftment and demonstrate the two defining features of stem cells, namely self-renewal and multipotency. We also show t...

متن کامل

Mesenchymal Stem Cells: History, Isolation and Biology

Mesenchymal stem cells (MSCs) as a kind of adult stem cells possess two properties of long term selfrenewal ability and multilineage differentiation potential into skeletal cell lineages. MSCs were first isolated and described from bone marrow samples. Further investigations have identified several other tissues as alternative sources for these cells. In spite of the clinical importance of MSCs...

متن کامل

The Level of the Transcription Factor Pax6 Is Essential for Controlling the Balance between Neural Stem Cell Self-Renewal and Neurogenesis

Neural stem cell self-renewal, neurogenesis, and cell fate determination are processes that control the generation of specific classes of neurons at the correct place and time. The transcription factor Pax6 is essential for neural stem cell proliferation, multipotency, and neurogenesis in many regions of the central nervous system, including the cerebral cortex. We used Pax6 as an entry point t...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 116  شماره 

صفحات  -

تاریخ انتشار 2017