We searched MEDLINE with the search terms differentiation, fusion, transdifferentiation, and transdetermination. Only papers in the English language were reviewed. Additional papers were identified through searches of the authors' own files.
ReviewAdult stem cells—reprogramming neurological repair?
Section snippets
Traditional stem-cell model
Pluripotent cells were first isolated from the embryonic inner cell mass.1 Ethical concerns, and the potential danger of teratoma formation, have contributed to the limited development of these cells as a therapeutic option: most scientists still talk in terms of “10–15 years”. However, adult stem cells have been used therapeutically for many years in malignant haematological disease and, more recently, for the treatment of inherited storage diseases. The haemopoietic stem cell has provided the
CNS stem cells
Neural stem cells have been identified in many species, including human beings.10, 11, 12, 13, 14 The discovery that progenitors attempt repair in human disease15, 16 has prompted the development of new theories to explain neurodegenerative disease,17 as well as offering hope that neurological repair could be enhanced via the supplementation, stimulation, or protection of endogenous precursors.18, 19 To detail the potential advantages of stem-cell therapy for particular neurological diseases is
Challenges to the hierarchical stem-cell model
Several findings challenge the traditional hierarchical model of tissue-specific adult stem cells.21, 22, 23 Bone-marrow-derived stem cells may have unexpected differentiation potential and can contribute to non-haemopoietic tissues. For example, donor-derived myocytes were found in mice after bone marrow transplantation;24 likewise, chimerism has been detected in the liver, brain, heart, and lungs of human recipients of bone-marrow transplants.25, 26, 27, 28, 29 Under conditions of strong
How adult stem cells might contribute to repair
At least six different mechanisms might be proposed: transdifferentiation, de-differentiation, transdetermination, cell fusion, true pluripotent stem-cell behaviour, and the production of trophic factors (figure 1). These mechanisms are, of course, not mutually exclusive.
Discussion
That cells previously thought to be of restricted lineage can give rise to progeny of different germ-cell lineages has questioned not only our understanding of stem-cell biology,115, 116, 117 but also wider issues pertaining to mechanisms of tissue homoeostasis and repair in the adult mammal.106 These issues have profound implications for reparative medicine.
To establish definitively the mechanism responsible for observed changes in cell phenotype, major technical difficulties must be overcome:
Search strategy and selection criteria
Conflict of interest statement
None declared.
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Cited by (70)
Stem Cell Biology
2017, Fetal and Neonatal Physiology, 2-Volume SetCell therapy for multiple sclerosis: An evolving concept with implications for other neurodegenerative diseases
2013, The LancetCitation Excerpt :First identified in bone marrow,36 mesenchymal stem cells can be found in many tissues—indeed, in every tissue in which they have been sought. Many researchers concentrate on bone-marrow-derived cells because of the increasing evidence that their normal function relates to tissue repair, and because the cells achieve this repair through several mechanisms, many of which are relevant to multiple sclerosis (figure 2).49,50 To develop a cell therapy based purely on exploitation of the normal function of the cells in question is intuitively attractive and logical.
Human bone marrow mesenchymal stem cells protect catecholaminergic and serotonergic neuronal perikarya and transporter function from oxidative stress by the secretion of glial-derived neurotrophic factor
2012, Brain ResearchCitation Excerpt :MSCs have generated some interest in the context of PD and other neurodegenerative diseases (Meyer et al., 2009; Whone and Scolding, 2009). There are various mechanisms by which MSCs may act in neurological diseases (Korbling and Estrov, 2003; Rice and Scolding, 2004). Replacement of lost cells through trans-differentiation into neurones and glia has produced great interest, but remains controversial (Barzilay et al., 2008; Bouchez et al., 2008).
Stem Cell Biology
2011, Fetal and Neonatal Physiology E-Book, Fourth EditionThe effect of repeated administrations of granulocyte colony stimulating factor for blood stem cells mobilization in patients with progressive supranuclear palsy, corticobasal degeneration and multiple system atrophy
2010, Clinical Neurology and NeurosurgeryCitation Excerpt :A recent randomized, blinded, controlled trial showed improvement in stroke patients treated with GCSF vs. standard care possibly through counteraction of acute neuronal degeneration and stimulation of neuronal plasticity [4]. Benefit may also result from a physiological stem cell repair system, whereby damaged cerebral areas may be able to signal to stem cells in the bone marrow and coax them to migrate [5,6]. We proposed GCSF treatment to 11 patients (six women) aged 54–76 years, suffering from multiple system atrophy (MSA n = 4), progressive supranuclear palsy (PSP n = 5) and corticobasal degeneration (CBD n = 2) diagnosed according to international criteria [7–9].
Preliminary Characterization of the Epigenetic Modulation in the Human Mesenchymal Stem Cells during Chondrogenic Process
2022, International Journal of Molecular Sciences