Review
Mesenchymal stem cells, cancer challenges and new directions

https://doi.org/10.1016/j.ejca.2014.02.011Get rights and content

Abstract

Therapeutic use of multipotent mesenchymal stromal stem cells (MSC) is a promising venue for a large number of degenerative diseases and cancer. Their availability from many different adult tissues, ease of expansion in culture, the ability to avoid immune rejection and their homing ability, are some of the properties of MSCs that make them a great resource for therapy. However, the challenges and risks for cell-based therapies are multifaceted. The blessing of cell culture expansion also comes with a burden. During in vitro expansion, stem cells experience a long replicative history and therefore, become subjected to damage from intracellular and extracellular influences. As previously shown cells that are manipulated to obtain an expanded replicative potential are prone to spontaneous transformation in culture. These manipulations help bypass the naturally built-in controls of the cell that govern the delicate balance between cell proliferation, senescence and carcinogenesis.

Because of this, there is a risk for patients receiving stem cells that are in vitro expanded. Whether these cells are genetically engineered or harbouring xenogenic compounds, they cannot truly be considered “safe” unless the cells are closely monitored.

In the present communication, we will focus on the therapeutic potential of the human mesenchymal stem cells (hMSC) with special focus on their use in cancer therapy. We will consider different mechanisms, by which stem cells can maintain telomeres and thereby the cell’s ability to be expanded in vitro, and also focus on a new therapeutic venue that utilises hMSCs as delivery vehicles in innovative new cancer treatments.

Section snippets

Stem cells

Stem cells are defined as unspecialised cells with theoretically indefinite capacity for proliferation and differentiation into various cell types. During their proliferation stem cells either divide to produce two daughter cells that are identical to the mother cell (symmetric division) or one cell that is identical to the mother cell and another cell which is more differentiated (asymmetric division). Both of the daughter cells can further divide and differentiate (Fig. 1).

Classification of

The therapeutic potential of stem cells

One of the main therapeutic applications of human stem cells is the generation of cells and tissues that can be used for organ regeneration. Today, donated organs and tissues are often used to replace damaged tissue, but the need for transplantable tissues and organs far outweighs the available supply. Stem cells, directed to differentiate into specific cell types, are an alternative to donated organs by offering a renewable cell source of replacement of cells and tissues.

The stem cell field

Concluding remarks

The conventional treatments for cancers, albeit valuable, are faced with many problems. These problems include specificity, toxicity and development of resistance to therapeutic agents – intrinsic or acquired. Use of MSCs and their tumour homing ability will not only address the specificity issue of cancer treatment but will also allow for the delivery of more potent and more tailored treatments (Fig. 2B). The use of MSCs will also be of value when resistance is an issue, as they can be used to

Conflict of interest statement

None declared.

References (84)

  • H.P. Zhou et al.

    Administration of donor-derived mesenchymal stem cells can prolong the survival of rat cardiac allograft

    Transplant Proc

    (2006 Nov)
  • S. Garcia et al.

    Pitfalls in spontaneous in vitro transformation of human mesenchymal stem cells

    Exp Cell Res

    (2010 May 15)
  • A. Torsvik et al.

    Comment to: “Spontaneous transformation of adult mesenchymal stem cells from cynomolgus macaques in vitro” by Z. Ren et al. Exp. Cell Res. 317 (2011) 2950-2957: spontaneous transformation of mesenchymal stem cells in culture: facts or fiction?

    Exp Cell Res

    (2012 Mar 10)
  • Z. Ren et al.

    Spontaneous transformation of adult mesenchymal stem cells from cynomolgus macaques in vitro

    Exp Cell Res

    (2011 Dec 10)
  • N. Serakinci et al.

    Ectopically hTERT expressing adult human mesenchymal stem cells are less radiosensitive than their telomerase negative counterpart

    Exp Cell Res

    (2007 Mar 10)
  • L. Barkholt et al.

    Risk of tumorigenicity in mesenchymal stromal cell-based therapies – bridging scientific observations and regulatory viewpoints

    Cytotherapy

    (2013 Jul)
  • G.M. Forbes et al.

    A phase 2 study of allogeneic mesenchymal stromal cells for luminal Crohn’s disease refractory to biologic therapy

    Clin Gastroenterol Hepatol

    (2014 Jan)
  • M.G. Kaplitt et al.

    Safety and tolerability of gene therapy with an adeno-associated virus (AAV) borne GAD gene for Parkinson’s disease: an open label, phase I trial

    Lancet

    (2007 Jun 23)
  • X.L. Sun et al.

    Molecular targeting of malignant glioma cells with an EphA2-specific immunotoxin delivered by human bone marrow-derived mesenchymal stem cells

    Cancer Lett

    (2011 Dec 22)
  • T. Doucette et al.

    Mesenchymal stem cells display tumor-specific tropism in an RCAS/Ntv-a glioma model

    Neoplasia

    (2011 Aug)
  • S. Duchi et al.

    Mesenchymal stem cells as delivery vehicle of porphyrin loaded nanoparticles: effective photoinduced in vitro killing of osteosarcoma

    J Controlled Release

    (2013 Jun 10)
  • M. Fakler et al.

    Small molecule XIAP inhibitors cooperate with TRAIL to induce apoptosis in childhood acute leukemia cells and overcome Bcl-2-mediated resistance

    Blood

    (2009 Feb 19)
  • R.S. Beddington et al.

    An assessment of the developmental potential of embryonic stem cells in the midgestation mouse embryo

    Development

    (1989 Apr)
  • A. Cumano et al.

    Bipotential precursors of B cells and macrophages in murine fetal liver

    Nature

    (1992 Apr 16)
  • J.E. Dennis et al.

    A quadripotential mesenchymal progenitor cell isolated from the marrow of an adult mouse

    J Bone Miner Res

    (1999 May)
  • C.S. Lantz et al.

    Differential responsiveness of purified mouse c-kit+ mast cells and their progenitors to IL-3 and stem cell factor

    J Immunol

    (1995 Oct 15)
  • M.S. Rao et al.

    A tripotential glial precursor cell is present in the developing spinal cord

    Proc Natl Acad Sci U S A

    (1998 Mar 31)
  • S. Sell

    Stem cells

  • J.A. Thomson et al.

    Embryonic stem cell lines derived from human blastocysts

    Science

    (1998 Nov 6)
  • P.J. Ho et al.

    Current applications of human pluripotent stem cells: possibilities and challenges

    Cell Transplant

    (2012)
  • K. Martins-Taylor et al.

    Concise review: genomic stability of human induced pluripotent stem cells

    Stem Cells

    (2012 Jan)
  • M. Buemi et al.

    A new therapy for kidney injury: regeneration

    Eur Rev Med Pharmacol Sci

    (2011 Feb)
  • G.A. Silva et al.

    Stem cell and tissue engineering therapies for ocular regeneration

    Curr Stem Cell Res Ther

    (2011 Sep)
  • M.F. Pittenger et al.

    Mesenchymal stem cells and their potential as cardiac therapeutics

    Circ Res

    (2004 Jul 9)
  • K. Rajala et al.

    Cardiac differentiation of pluripotent stem cells

    Stem Cells Int

    (2011)
  • T. Winkler et al.

    Immediate and delayed transplantation of mesenchymal stem cells improve muscle force after skeletal muscle injury in rats

    J Tissue Eng Regen Med

    (2012 Dec)
  • R.F. Ambinder

    The same but different: autologous hematopoietic stem cell transplantation for patients with lymphoma and HIV infection

    Bone Marrow Transplant

    (2009 Jul)
  • M. Schaaf et al.

    High-dose therapy with autologous stem cell transplantation versus chemotherapy or immuno-chemotherapy for follicular lymphoma in adults

    Cochrane Database Syst Rev

    (2012)
  • M.S. Tsai et al.

    Isolation of human multipotent mesenchymal stem cells from second-trimester amniotic fluid using a novel two-stage culture protocol

    Hum Reprod

    (2004 Jun)
  • M.L. Weiss et al.

    Stem cells in the umbilical cord

    Stem Cell Rev

    (2006)
  • N.J. Zvaifler et al.

    Mesenchymal precursor cells in the blood of normal individuals

    Arthritis Res

    (2000)
  • F.H. Chen et al.

    Mesenchymal stem cells in arthritic diseases

    Arthritis Res Ther

    (2008)
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