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PubMed2005

Stem cell plasticity and issues of stem cell therapy.

Today, there is much evidence suggesting that organ-specific stem cells need not rely completely on their own sources for maintenance and regeneration of an organism. In certain circumstances, mostly related to tissue damage, stem cell populations residing past the affected organ can contribute to its recovery--that means from different cell lines and also in tissues from another germ layer. The key factor in formation of self-renewing cellular clones is the presence of stem cells either from the tissue of origin or stem cells migrating from other areas and their successful settlement in an empty niche of the damaged tissue. Stem cell plasticity is the ability of adult tissue-specific stem cells to switch to new identities. The term plasticity also means stem cell phenotypic potential, which is broader than phenotypes of differentiated cells in their original tissues. Many laboratories have given evidence on stem cell plasticity; however, the presented results met with many objections from others. In the first part of our report we wish to refer to several issues associated with stem cell plasticity, transdifferentiation and fusion. Recent experimental results show that stem cells will play a key role in cell therapy. But there are still many questions to answer for scientists engaged in stem cell research. Is it possible to induce cells from one type of tissue to look and act as cells of another tissue? Do these changes occur naturally? Could plasticity be used in the treatment of fatal diseases? Cell therapy is one of the methods to treat damaged myocardial tissue. However, recent results with autologous bone marrow cells in the treatment of damaged myocardium show that this method has still many unanswered questions concerning cells, cytokines, microenvironment and other factors responsible for reparation. To date, there are many opinions either recommending or denying this method in different modifications. One question has not yet been definitely solved: What are the conditions for us to accept this method--its safety and efficacy? The future will show whether these our hopes and expectations will be fulfiled. Many experiments are needed before at least some of these questions may be answered and cell therapy become an important method for the benefit of our patients.

Cell Differentiation↗
PubMed1998

Prolactin-producing cells differentiate from G0/G1-arrested somatotrophs in vitro: an analysis of cell cycle phases and mammotroph differentiation.

In order to analyze the relationship between cell proliferation and mammotroph differentiation, we studied a somatotrophic cell line, MtT/S. MtT/S cell is known to differentiate into PRL-producing cells in response to stimulation with insulin or insulin-like growth factor-1 (IGF-1). Double immunostaining for bromodeoxyuridine (BrdU), which labels proliferating cells, and for GH or PRL showed that most BrdU-labeled cells were GH-immunopositive, whereas considerably few PRL-positive cells were labeled with BrdU. This was confirmed by immunostaining of proliferating cells with antibody to proliferating cell nuclear antigen (PCNA). Furthermore, flow-cytometry analysis indicated that most of the PRL-producing cells were in the G0/G1 phase of the cell cycle. In order to determine whether cell cycle changes are required for transdifferentiation of PRL-producing cells, MtT/S cells were cultivated in serum restricted medium for 7 days to reduce their mitotic activity and then treated with insulin and epidermal growth factor (EGF). Under these conditions, the cell cycle of MtT/S cells was significantly delayed, but the percentage of PRL-producing cells induced was almost identical to that under control conditions, showing that mitosis is not required for PRL- producing cell differentiation. We also labeled MtT/S cells with BrdU for 24 h during PRL-producing cell induction by insulin and EGF, and as a result BrdU-labeled proliferative cells were specifically absent from PRL-producing cell populations. These data, taken as whole, suggest that PRL cells differentiated from G0/G1 arrested somatotrophs and the PRL cells which appeared had their cell proliferation activity significantly declined. In conclusion, this is the first report showing the relationship cell between proliferation and differentiation of PRL cells.

Animals↗
PubMed2003

Thiazolidinediones -- some recent developments.

The role of thiazolidinediones (currently rosiglitazone and pioglitazone) in the treatment of Type 2 diabetes is firmly established. The mechanism of action involves binding to the peroxisome proliferator-activated receptor-gamma, a transcription factor that regulates the expression of specific genes especially in fat cells but also other cell types such as endothelial cells, macrophages and monocytes, vascular smooth muscle cells and colonic epithelium. Thiazolidinediones have been shown to interfere with expression and release of mediators of insulin resistance originating in adipose tissue (e.g., increased free fatty acids, decreased adiponectin) in a way that results in net improvement of insulin sensitivity (i.e., in muscle and liver). A direct or indirect effect on AMP-dependent protein kinase may also be involved. Prevention of lipid accumulation in tissues critical to glycaemia such as visceral adipocytes, liver, muscle and beta-cells at the expense of lipids accumulating at the less harmful subcutaneous site may be central to their net metabolic effect. The sustained beneficial effect of troglitazone on beta-cell function in women with previous gestational diabetes in addition to the insulin-sensitising properties point to an important role of this class of drugs in the prevention of Type 2 diabetes. Original safety concerns based on animal and in vitro studies (e.g., fatty bone marrow transformation, colonic cancer, adipogenic transdifferentiation of blood cells) remain theoretical issues but become less pressing practically with prolonged uneventful clinical use. Hepatotoxicity for troglitazone and fluid retention, which can aggravate pre-existing heart failure, are the most important side effects. In summary, with the thiazolidinediones, a novel concept for the treatment of insulin resistance and possibly preservation of beta-cell function is available that could become effective in the prevention of Type 2 diabetes. Moreover, their anti-inflammatory properties also make them interesting in the prevention and treatment of atherosclerosis and possibly other inflammatory conditions (e.g., inflammatory bowel disease). Long-term data will be necessary for a final risk-benefit assessment of these substances.

Adipose Tissue↗
PubMed2004

Embryonic committed stem cells as a solution to kidney donor shortage.

The number of human kidney transplants has increased rapidly in recent years, but the need greatly exceeds organ availability. Induction of appropriate kidney differentiation and growth from stem or progenitor cell populations represents an attractive option to combat chronic kidney donor shortage. In an analogy to haematopoietic stem cells, which are much more efficient in giving rise to blood than to other cell types, if any at all, renal stem cells could afford an unlimited source for regenerating nephrons. While a single nephrogenic stem cell has not been characterised, indirect evidence suggests that a renal stem cell population is contained within the metanephric mesenchyme, which along with a branch of the Wolffian duct represents the direct precursor of the mature kidney. Human tissue fragments derived from these developing precursors can regenerate renal structures when grafted into mice. Moreover, recent data pinpoints a window of time in human and pig kidney development that may be optimal for transplantation into mature recipients. 'Window' transplants are defined by their remarkable ability to grow, differentiate and undergo vascularisation, achieving successful organogenesis of urine-producing miniature kidneys with no evidence of transdifferentiation into non-renal cell types, lack of tumourigenicity and reduced immunogenicity compared with adult counterparts. In contrast, 'non-window' transplants (earlier or later in gestation) can form teratomas or are more prone to immune rejection and are less suitable for organogenesis. Hopefully, the use of stage-specific early human and porcine kidney precursors to cultivate mature kidney cells in vivo, possibly in conjunction with other modalities of stem cell technology and tissue engineering, will prove valuable to sustain life in patients with failing kidneys.

Animals↗
PubMed2004

Keystone symposia - stem cells.

The Keystone Symposia stem cell conference focused on the biological nature of self-renewing cell populations that exist in special regulatory niches and form other cell types that enable maintenance of tissue function, repair and, in some cases, regeneration. Adult stem cells are present in most, if not all tissues, and their regulation as renewing populations, the nature of the niche and the factors driving decisions for differentiation in primary pathways remain the dominant interest in the field. The more vexed question concerning possible transdifferentiation of adult stem cells from one tissue type to another has become focused on the role of fusion and whether this is a recapitulation of normal processes in embryonic and adult development. The possible linkage of cancer phenotypes with stem cells and downstream progenitor cell types through loss of regulatory influences in renewal, expansion and lineage commitment is a rapidly growing interest. Pluripotent embryonic stem (ES) cells and their maintenance and directed differentiation into a variety of tissue types remains an optimistic field of research in which some debate exists about true pluripotency of adult stem cells. The role of epigenetic influences on differentiation and development has drawn on data from nuclear transfer studies in cloning the whole organism and in ES cell production. The formation of germ cells and their renewal and differentiation was also a major interest of the symposium.

Animals↗
PubMed2004

Gene therapy for proliferative ocular diseases.

Proliferative ocular diseases encompass a wide variety of pathological processes with adverse cellular differentiation, proliferation and migration as common features. Pathologies may involve neovascular responses associated with diabetic retinopathy, retinopathy of prematurity or age-related macular degeneration. These diseases are quite prevalent and account for substantial visual impairment and blindness worldwide. Although treatment strategies are largely surgical, advances in our understanding of the proteins crucial to cell transdifferentiation, proliferation and migration, along with better gene transfer techniques, have greatly increased the potential for biological treatment options. In this report, the most common proliferative ocular vascular diseases and existing therapeutic modalities will be reviewed and an overview of possible gene therapy options will be discussed, along with potential candidate genes.

Adenoviridae↗
PubMed2004

A role of ath5 in inducing neuroD and the photoreceptor pathway.

Photoreceptors in the vertebrate retina are light-sensitive neurons, and their degeneration results in irreversible visual loss. Understanding how photoreceptor fate is determined is a prerequisite for developing photoreceptor replacement therapies. Previous studies identified two basic helix-loop-helix genes, neurogenin2 (ngn2) and neuroD, participating in a genetic pathway leading to photoreceptor genesis. Here we present experimental data suggesting that ath5, which is known for its critical role in retinal ganglion cell development, may also lead to photoreceptor production. In the developing retina, ath5 expression was detected in two zones of cells, and coexpression with neuroD was observed in the zone adjacent to young photoreceptor cells accumulating on the retinal pigment epithelial side. Retroviral-driven misexpression of ath5 in retinal cells increased the population of photoreceptor cells, as well as ganglion cells, in a developmental stage-dependent manner that is consistent with ath5 being involved in the development of multiple types of retinal neurons. Ectopic ath5 expression in cultures of non-neural retinal pigment epithelial cells elicited transdifferentiation into cells that expressed photoreceptor-specific genes and displayed photoreceptor-like morphologies. Gene expression analysis showed that ngn2 did not induce ath5, and ath5 did not induce ngn2, but both induced neuroD and RaxL. These data suggest a pathway of "ath5 --> neuroD --> photoreceptor genes" separate from yet convergent with the ngn2 pathway.

Animals↗
PubMed2006

Regeneration of vestibular otolith afferents after ototoxic damage.

Regeneration of receptor cells and subsequent functional recovery after damage in the auditory and vestibular systems of many vertebrates is well known. Spontaneous regeneration of mammalian hair cells does not occur. However, recent approaches provide hope for similar restoration of hearing and balance in humans after loss. Newly regenerated hair cells receive afferent terminal contacts, yet nothing is known about how reinnervation progresses or whether regenerated afferents finally develop normal termination fields. We hypothesized that neural regeneration in the vestibular otolith system would recapitulate the topographic phenotype of afferent innervation so characteristic of normal development. We used an ototoxic agent to produce complete vestibular receptor cell loss and epithelial denervation, and then quantitatively examined afferent regeneration at discrete periods up to 1 year in otolith maculas. Here, we report that bouton, dimorph, and calyx afferents all regenerate slowly at different time epochs, through a progressive temporal sequence. Furthermore, our data suggest that both the hair cells and their innervating afferents transdifferentiate from an early form into more advanced forms during regeneration. Finally, we show that regeneration remarkably recapitulates the topographic organization of afferent macular innervation, comparable with that developed through normative morphogenesis. However, we also show that regenerated terminal morphologies were significantly less complex than normal fibers. Whether these structural fiber changes lead to alterations in afferent responsiveness is unknown. If true, adaptive plasticity in the central neural processing of motion information would be necessitated, because it is known that many vestibular-related behaviors fully recover during regeneration.

Acoustic Maculae↗
PubMed2003

Enhanced anterior pituitary mitotic response to adrenalectomy after multiple glucocorticoid exposures.

OBJECTIVES: Glucocorticoid withdrawal in man is associated with transient but sometimes prolonged impairment of hypothalamo-pituitary-adrenal axis secretory responsiveness. This has led to continued concern in the clinical arena. The acute anterior pituitary response to glucocorticoids in the rat includes apoptosis-mediated deletion of a cell population. Whilst continued cell turnover following glucocorticoid withdrawal and the potential for differentiation of uncommitted precursor cells and transdifferentiation of other secretory cell types predicts that, given sufficient time, complete anterior pituitary trophic recovery is likely, this hypothesis has not previously been tested. DESIGN AND METHODS: We have quantified pituitary mitotic and apoptotic rate, as well as corticotroph number and pro-opiomelanocortin transcript prevalence, together with hypothalamic corticotrophin-releasing hormone and vasopressin transcript prevalence 5 weeks after three short dexamethasone treatments each separated by a week. Bilateral adrenalectomy was then carried out as a maximal secretory and trophic stimulus, and the response to a fourth dexamethasone treatment assessed 1 week later. RESULTS: Anterior pituitary mitotic index was significantly higher in rats previously exposed to dexamethasone compared with age-matched controls exposed to dexamethasone for the first time. No differences were found in the subsequent apoptotic response to a fourth dexamethasone treatment or in the levels of paraventricular corticotrophin-releasing hormone or vasopressin transcripts or pituitary pro-opiomelanocortin transcripts. CONCLUSIONS: These data indicate that full recovery of pituitary mitotic activity takes longer than the recovery of secretory parameters, and suggest that, for several weeks after glucocorticoid exposure, the ability of the pituitary to meet fresh demands placed on it may be suboptimal.

Adrenalectomy↗
PubMed1988

Persistent infertility in ewes after prolonged exposure to oestradiol-17 beta.

Merino ewes were treated with implants which released 300 micrograms oestradiol-17 beta per day or 5 mg progesterone per day, or both, for 9 months (Months 1-9), and after an 11-month intermission were treated again for 6 months (Months 20-26). Ewes were run with rams at Months 16, 28 and 40. Fertility was not affected by the first exposure period, but the second exposure to oestradiol reduced the fertility of ewes at both subsequent mating periods. Affected ewes returned to service more frequently (P less than 0.01) and were less likely to conceive (P less than 0.05). After mating, a normal population of spermatozoa was established in the caudal cervix, but transport through the cervix was impaired in affected ewes and there were fewer spermatozoa (P less than 0.01) in the cranial cervix. In affected ewes, the spinnbarkeit of cervical mucus was reduced (P less than 0.05), and the histological appearance of the cervix changed, looking like that of the uterus. Treatment with progesterone did not affect fertility, cervical mucus or sperm transport, but diminished the histological abnormalities produced by oestradiol (P less than 0.05). These results show that oestradiol-17 beta given after puberty can cause the same kind of permanent sexual transdifferentiation that is produced by the oestrogenic isoflavones in ewes with clover disease. The results suggest that this change may require more than a single exposure to oestrogen.

Animals↗
PubMed2003

Establishment of a recombinant expression system for connective tissue growth factor (CTGF) that models CTGF processing in utero.

Connective tissue growth factor (CTGF) stimulates cell proliferation, migration, adhesion and extracellular matrix production, and functions in processes such as development, differentiation, angiogenesis, implantation, wound healing and fibrosis. CTGF is a 38 kDa protein that comprises four discrete structural modules (modules 1-4) but is susceptible to limited proteolysis in utero yielding bioactive isoforms that comprise either modules 3 and 4 (16-20 kDa) or module 4 (10 kDa). Here we report the development of a stable cell line, termed DB1, that was generated by transfecting cDNA encoding full-length human CTGF into Chinese hamster ovary cells that were mutant for heparin sulphate and chondroitin sulphate. DB1 cells produced 38 kDa CTGF and low molecular mass CTGFs that had N-termini between modules 2 and 3 at Ala(181) (20 kDa), Leu(184) (18 kDa) or Ala(197) (16 kDa) or between modules 3 and 4 at Gly(253) (10 kDa). CTGF was exported from DB1 cells as early as 5 min after synthesis and all isoforms were readily purified from conditioned medium by sequential steps of heparin affinity, cation exchange, and reverse-phase chromatography. The 38 kDa CTGF was faithfully glycosylated and underwent limited proteolysis in the presence of thrombin, kallikrein or uterine fluids, the last of which was antagonized by anti-thrombin III. All CTGF isoforms promoted cell adhesion, mitosis and epithelial transdifferentiation in vitro as well as subcutaneous fibrosis in vivo. The establishment of this recombinant expression system allows for mass-scale production of all previously reported uterine CTGF isoforms, demonstrates that module 4 contains functional domains involved in a broad range of biological activities, and will facilitate studies of CTGF processing in vitro.

Animals↗
PubMed2005

mTOR promotes survival and astrocytic characteristics induced by Pten/AKT signaling in glioblastoma.

Combined activation of Ras and AKT leads to the formation of astrocytic glioblastoma multiforme (GBM) in mice. In human GBMs, AKT is not mutated but is activated in approximately 70% of these tumors, in association with loss of PTEN and/or activation of receptor tyrosine kinases. Mechanistic justification for the therapeutic blockade of targets downstream of AKT, such as mTOR, in these cancers requires demonstration that the oncogenic effect of PTEN loss is through elevated AKT activity. We demonstrate here that loss of Pten is similar to AKT activation in the context of glioma formation in mice. We further delineate the role of mTOR activity downstream of AKT in the maintenance of AKT+KRas-induced GBMs. Blockade of mTOR results in regional apoptosis in these tumors and conversion in the character of surviving tumor cells from astrocytoma to oligodendroglioma. These data suggest that mTOR activity is required for the survival of some cells within these GBMs, and mTOR appears required for the maintenance of astrocytic character in the surviving cells. Furthermore, our study provides the first example of conversion between two distinct tumor types usually thought of as belonging to specific lineages, and provides evidence for signal transduction-mediated transdifferentiation between glioma subtypes.

Animals↗
PubMed2002

Toward pathogenesis of Apert cleft palate: FGF, FGFR, and TGF beta genes are differentially expressed in sequential stages of human palatal shelf fusion.

OBJECTIVE: Critical cellular events at the palatal medial edge epithelium (MEE) occur in unperturbed mammalian palatogenesis, the molecular control of which involves a number of growth factors including transforming growth factor beta 3 (TGF beta 3). Apert syndrome is a monogenic human disorder in which cleft palate has been significantly correlated to the fibroblast growth factor receptor (FGFR) 2-Ser252Trp mutation. We report the relative expression of these genes in human palatogenesis. METHODS: The expression of the IgIIIa/b and IgIIIa/c transcript isoforms of FGFR2 and the proteins FGFR1, FGFR2, and FGFR3 was studied in situ throughout the temporospatial sequence of human palatal shelf fusion and correlated with the expression of TGF beta 3. In addition, the immunolocalization of the ligand FGFs 2, 4, and 7 was undertaken together with the intracellular transcription factor STAT1, which is activated by FGFR signaling. RESULTS: FGFRs are differentially expressed in the mesenchyme and epithelia of fusing palatal shelves, in domains overlapping those of their ligands FGF4 and FGF2 but not FGF7. Coexpression is seen with TGF beta 3, which is implicated in MEE dynamics and FGF and FGFR upregulation, and STAT1, an intracellular transcription factor that mediates apoptosis. CONCLUSIONS: The coregulation of molecules of the FGFR signaling pathway with TGF beta 3 throughout the stages of human palatal fusion suggests their controlling influence on apoptosis and epitheliomesenchymal transdifferentiation at the MEE. Experimental evidence links FGFR2-IgIIIa/b loss of function with palatal clefting, and these correlated data suggest a unique pathological mechanism for Apert cleft palate.

Acrocephalosyndactylia↗
PubMed1994

Retrodifferentiation and cell death.

The reversibility of a differentiation program termed dedifferentiation, redifferentiation, or retrodifferentiation opens a spectrum of new possibilities for cellular development. During differentiation and retrodifferentiation, the expression of gene products associated with a differentiated phenotype and cell cycle regulation demonstrate inverse patterns. This effect requires a coordinated network that simultaneously controls cell growth and differentiation. In particular, crosstalk between induction of differentiation and G0/G1 cell cycle exit can be initiated and sustained by activated serine/threonine kinases and tyrosine kinases. Phosphorylation signals are relayed to certain genes or transcription factors such as Fos/Jun, EGR-1, NF-kappa B, MyoD, or the Myc/Max gene family. However, the precise regulation of these transcription factors to confer signals to differentiation-associated and cell cycle-regulatory genes remains unclear. Cell cycle exit into a transient G0'-arrest cycle or a terminal G0 phase is determined by a network of phosphorylation signals involving the retinoblastoma protein and a variety of factors such as the E2F family, cyclins, and cyclin-dependent kinases. In this context, a variety of differentiation-induced cell lines, including monocytic, neuronal, or muscle cells, can progress through the G0'-arrest cycle, whereby a certain population retains the capacity to retrodifferentiate and reenter the cell cycle. In contrast, the rest of the differentiated population enters the irreversible G0 phase (terminal commitment) that finally results in programmed cell death. The expression of growth arrest-specific (gas and gadd) genes is associated with the G0'-arrest cycle, and other factors, including c-myc, p53, mdm2, and bcl2/bclx, contribute to the regulation of the cell death program. Although the precise signaling cascade determining retrodifferentiation or cell death remains unclear, a coordinated inter- and intracellular regulation could establish a certain biological balance between these exclusive pathways. Consequently, a retrodifferentiation process may provide a potential for cell type conversion or transdifferentiation, whereby retrodifferentiated cells can be induced to develop via a different pathway according to tissue-specific requirements.

Animals↗
PubMed2004

In vitro cultured islet-derived progenitor cells of human origin express human albumin in severe combined immunodeficiency mouse liver in vivo.

Studies in rodents suggest the presence of a hepatopancreatic stem cell in adult pancreas that may give rise to liver cells in vivo. The aim of the present study was to determine the ability of human islet-derived cells to adopt a hepatic phenotype in vivo. Cultured human islet-derived progenitor cells that did not express albumin in vitro were stained with the red fluorescent dye PKH26 and injected into the liver of severe combined immunodeficiency mice. After 3 or 12 weeks, red fluorescent cells were detected in 11 of 15 livers and were mostly single cells that were well integrated into the liver tissue. Human albumin was found in 8 of 11 animals by immunohistochemistry, and human albumin mRNA was detected in 4 of 10 host livers. The mechanism underlying this phenomenon seems to be transdifferentiation, because human and mouse albumin were found to be expressed in distinct cells in the host liver.

Albumins↗
PubMed2005

Isolation and characterization of neurogenic mesenchymal stem cells in human scalp tissue.

Recent studies have shown that adult tissues contain stem/ progenitor cells capable of not only generating mature cells of their tissue of origin but also transdifferentiating themselves into other tissue cells. Murine skin-derived precursor cells, for example, have been described as unique, nonmesenchymal-like stem cells capable of mesodermal and ectodermal neurogenic differentiation. Human-derived skin precursors are less well characterized. In this study, the isolation and characterization of adherent, mesenchymal stem cell-like cells from human scalp tissue (hSCPs) are described. hSCPs initially isolated by both medium-selection (ms-hSCPs) and single-cell (c-hSCPs) methods were cultured in medium containing epidermal growth factor and fibroblast growth factor-beta. Cultured ms-hSCPs and c-hSCPs demonstrated a consistent growth rate, continuously replicated in cell culture, and displayed a stable phenotype indistinguishable from each other. Both hSCPs expressed surface antigen profile (CDw90, SH2, SH4, CD105, CD166, CD44, CD49d-e, and HLA class I) similar to that of bone marrow mesenchymal stem cells (BM-MSCs). The growth kinetics, surface epitopes, and differentiation potential of c-hSCP cells were characterized and compared with BM-MSCs. In addition to differentiation along the osteogenic, chondrogenic, and adipogenic lineages, hSCPs can effectively differentiate into neuronal precursors evident by neurogenic gene expression of glial fibrillary acid protein, NCAM, neuron filament-M, and microtubule-associated protein 2 transcripts. Therefore, hSCPs may potentially be a better alternative of BM-MSCs for neural repairing, in addition to their other mesenchymal regenerative capacity. Our study suggests that hSCPs may provide an alternative adult stem cell resource that may be useful for regenerative tissue repair and autotransplantations.

Adipocytes↗
PubMed2005

Human umbilical cord blood progenitors: the potential of these hematopoietic cells to become neural.

The mononuclear fraction from human umbilical cord blood (HUCB) contains a significant number of stem/progenitor cells that in theory could be come any cell in the body, including neurons. Taking into consideration that transdifferentiation would be a very rare event and also knowing that overlapping genetic programs for hematopoiesis and neuropoiesis exist, we undertook a characterization of the HUCB mononuclear fraction, including analysis of cellular subpopulations and their morphology, cell viability, proliferation, and expression of neural and hematopoietic antigens. Two cell populations were apparent-adherent and floating fractions. The adherent fraction was mainly lymphocytes (~53%) expressing hematopoietic antigens. Upon replate, the floating population had many cells that expressed stem cell antigens. More of the cells in this subfraction expressed neural proteins. Neurotrophin receptors trkB and trkC were present in both cell fractions, although expression was higher in the floating fraction. Our initial characterization suggests that a subpopulation of cells exists within the HUCB mononuclear fraction that seems to have the potential to become neural cells, which could then be used in the development of cell-based therapies for brain injuries and diseases.

Antigens, CD↗
PubMed2005

Bone marrow lacks a transplantable progenitor for smooth muscle type alpha-actin-expressing cells.

While some studies have suggested that hematopoietic stem cells might give rise to other tissue types, others indicate that transdifferentiation would have to be an extremely rare event. We have now exploited smooth muscle type alpha-actin (alphaSMA) promoter-driven green fluorescent protein (GFP) transgenic mice (alphaSMA-GFP mice) for bone marrow transplantation to evaluate their potential to generate donor-type tissues in irradiation chimeras. There was a highly restricted pattern of GFP expression in the transgenic mice, marking bone marrow stromal cells and mesangial cells in the kidney. However, these characteristics were not transferable to wild-type animals given transgenic marrow cells even though hematopoietic cells were largely replaced. Our findings support earlier studies suggesting that the bone marrow microenvironment is difficult to transplant and indicate that hematopoietic stem cells are unlikely to give rise to alphaSMA-expressing progeny.

Actins↗