Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Stemness”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources
PubMed1996

Outcome of revision for mechanical stem failure using the cemented Charnley's stem. A study of 399 cases.

Three hundred ninety-nine cemented stem revision total hip arthroplasties performed in cases with mechanical stem failure without infection and having a minimum follow-up period of 3 years were prospectively studied. Two hundred eighty-three were revised for aseptic stem loosening and 116 were revised for fractured stem. Bone-grafting was not performed in any of the cases. The average follow-up period was 7 years 5 months. At the last follow-up evaluation, 70.4% of the patients were pain free and 20.6% had only mild or occasional discomfort. On radiographic evaluation, 31 stems (7.8%) were loose. Thirty-five hips (8.8%) required a rerevision, of which only 20 (5.0%) were for recurrence of mechanical stem failure. Clinical survivorship of the revised stem was 93.9% at 10 years, whereas radiographic survivorship was 91.5% at 10 years. On radiographic analysis, the mechanical failure rate at the last follow-up evaluation was greater after revision for fractured stem than after revision for aseptic stem loosening. Prerevision femoral cortical bone stock did not appear to adversely affect the outcome of the procedure. The clinical and radiologic results achieved with cemented stem revision arthroplasty for mechanical stem failure are excellent.

Adult↗
PubMed2005

Stem cell medicine: umbilical cord blood and its stem cell potential.

The ultimate aim of stem cell research is to improve patient outcomes and quality of life, and/or to effect a cure for a variety of inherited or acquired diseases. Improved treatments rely on developments in stem cell therapies and the discovery of new therapeutic drugs that regulate stem cell functions. These complement each other for the repair, regeneration and replacement of damaged or defective tissues. Stem cells may be sourced or derived from blood and tissues postnatally ('adult' stem cells), from the fetus (fetal stem cells) or from the blastocyst in the developing embryo prior to implantation (embryonic stem cells), each forming a unique component of the revolution in stem cell research and therapies. This review will concentrate on recent developments in the use of haemopoietic stem cells from umbilical cord blood for the transplantation of patients with haematological disorders. It will conclude with a summary of the potential of other umbilical cord blood-derived stem cells for tissue repair or regeneration.

Animals↗
PubMed2004

The bone marrow is akin to skin: HCELL and the biology of hematopoietic stem cell homing.

The recent findings that adult stem cells are capable of generating new blood vessels and parenchymal cells within tissues they have colonized has raised immense optimism that these cells may provide functional recovery of damaged organs. The use of adult stem cells for regenerative therapy poses the challenging task of getting these cells into the requisite sites with minimum morbidity and maximum efficiency. Ideally, tissue-specific colonization could be achieved by introducing the stem cells intravascularly and exploiting the native physiologic processes governing cell trafficking. Critical to the success of this approach is the use of stem cells bearing appropriate membrane molecules that mediate homing from vascular to tissue compartments. Hematopoietic stem cells (HSC) express a novel glycoform of CD44 known as hematopoietic cell E-/L-selectin ligand (HCELL). This molecule is the most potent E-selectin ligand natively expressed on any human cell. This article reviews our current understanding of the molecular basis of HSC homing and will describe the fundamental "roll" of HCELL in opening the avenues for efficient HSC trafficking to the bone marrow, the skin and other extramedullary sites.

Animals↗
PubMed2006

Stem cell protein Piwil2 modulates expression of murine spermatogonial stem cell expressed genes.

The piwi family genes are highly conserved during evolution and play essential roles in stem cell self-renewal, gametogenesis, and RNA interference in diverse organisms ranging from Arabidopsis to human. Piwil2, known also as Mili gene, is one of three mouse homologues of piwi. Piwil2 was found in germ cells of adult testis, suggesting that this gene functions in spermatogonial stem cell self-renewal. In order to find molecular mechanisms underlying stem cell activity mediated by Piwil2 gene, an in vitro gain of function cell culture model was established. Messenger RNAs isolated from cells expressing Piwil2 and mRNAs isolated from cells without Piwil2 expression were compared using a stem cell array technique. It was shown that Piwil2 modulates expression of stem cell specific genes, including platelet-derived growth factor receptor, beta polypeptide (Pdgfrb), solute carrier family 2 member 1 (Slc2a1), gap junction membrane channel protein alpha 7 (Gja7), and spermatogonial cell surface markers Thy-1 (CD90), integrin alpha 6 (Itga6), CD9, and spermatogonia specific markers heat shock protein 90 alpha (Hsp90a), and stimulated by retinoic acid gene 8 (Stra8). These molecules play essential role in stem cells proliferation (Pdgfrb), energy metabolism (Slc2a1), cell adhesion, cell-cell interaction (Itga6, Gja7, Thy-1, and CD9), and germ cell differentiation (Stra8). The expression of these markers in spermatogonial stem cells and other nongerminal stem cells suggests that these cells share elements of common molecular machinery with stem cells in other tissues which are modulated by stem cell protein Piwil2.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Identification of differentially expressed transcripts from maturing stem of sugarcane by in silico analysis of stem expressed sequence tags and gene expression profiling.

Sugarcane accumulates high concentrations of sucrose in the mature stem and a number of physiological processes on-going in maturing stem tissue both directly and indirectly allow this process. To identify transcripts that are associated with stem maturation, we compared patterns of gene expression in maturing and immature stem tissue by expression profiling and bioinformatic analysis of sets of stem ESTs. This study complements a previous study of gene expression associated directly with sugar metabolism in sugarcane. A survey of sequences derived from stem tissue identified an abundance of several classes of sequence that are associated with fibre biosynthesis in the maturing stem. A combination of EST analyses and microarray hybridization revealed that genes encoding homologues of the dirigent protein, a protein that assists in the stereospecificity of lignin assembly, were the most abundant and most strongly differentially expressed transcripts in maturing stem tissue. There was also evidence of coordinated expression of other categories of fibre biosynthesis and putative defence- and stress-related transcripts in the maturing stem. This study has demonstrated the utility of genomic approaches using large-scale EST acquisition and microarray hybridization techniques to highlight the very significant transcriptional investment the maturing stem of sugarcane has placed in fibre biosynthesis and stress tolerance, in addition to its already well-documented role in sugar accumulation.

Amino Acid Sequence↗
PubMed2004

Relationships between stem cells and cancer stem cells.

Stem cells have been shown to exist in a variety of tissues. Recent studies have characterized stem cell gene expression patterns, phenotypes, and potential therapeutic uses. One of the most important properties of stem cells is that of self renewal. This raises the possibility that some of the clinical properties of human tumors may be due to transformed stem cells. Similar signaling pathways may regulate self renewal in normal and transformed stem cells. These rare transformed stem cells may drive the process of tumorigenesis due to their potential for self renewal. There are important ramifications for clinical cancer treatment if the growth of solid tumors is at least partially dependent on a cancer stem cell population. In the cancer stem cell model, tumor recurrence may be due to the non-targeted stem cell compartment repopulating the tumor. If cancer stem cells can be prospectively identified and isolated, it should be possible to identify therapies that will selectively target these cells.

Animals↗
PubMed2003

[Culture of neural stem cells from cerebral cortex of rat embryo and effects of drugs on the proliferation ability of stem cells].

AIM: To establish culture procedures of neural stem cells from embryonic rat brain, determine their stem-cell characteristics and observe the effects of several compounds on their proliferation ability. METHODS: Firstly, a stem cell culture system was set up from embryonic rat cortex. The cells were identified as neural stem cells through immunocytochemistry, in which antibodies to neural stem cell specific protein and markers of mature neural cells were used. Then, by using MTT assay, the survival rate of neurospheres incubated with various concentrations of ginsenoside Rg1, (-)-clausenamide and salvianolic acid A were observed. Furthermore, the effect of these drugs was measured with 3[H] thymidine incorporation assay. RESULTS: In this study, a culture model of neural stem cell was successfully set up. In this model, primary cells from E16-18 rat cortex were dissected out, and cultured as floating neurospheres. The results of immunocytochemistry showed that nestin was expressed by the majority of cells within the sphere. After growing for 8 days in differentiation medium, cells from a single neurosphere were shown to differentiate into 3 main kinds of neural cells: neurons, astrocytes and oligodendrocytes. MTT assay revealed that the three drugs all enhanced the survival rate of neural stem cells, but 3[H] thymidine incorporation assay suggested that only Rg1 significantly accelerated the proliferation rate. CONCLUSION: One culture model of neural stem cell was set up successfully. Meanwhile, several drugs were found to increase the proliferation and/or survival rate of neural stem cells. It has been demonstrated that neural stem cells exist in adult mammalian brains. So, these drugs may become promising candidates for the therapy of neurodegenerative diseases; such as Alzheimer's disease and Parkinson's disease.

Animals↗
PubMed1998

Stroma-contact prevents loss of hematopoietic stem cell quality during ex vivo expansion of CD34+ mobilized peripheral blood stem cells.

Stroma-supported long-term cultures (LTC) allow estimation of stem cell quality by simultaneous enumeration of hematopoietic stem cell (HSC) frequencies in a graft using the cobblestone area forming cell (CAFC) assay, and the ability of the graft to generate progenitors in flask LTC (LTC-CFC). We have recently observed that the number and quality of mobilized peripheral blood stem cells (PBSC) was low in patients having received multiple rounds of chemotherapy. Moreover, grafts with low numbers of HSC and poor HSC quality had a high probability to cause graft failure upon their autologous infusion. Because ex vivo culture of stem cells has been suggested to present an attractive tool to improve hematological recovery or reduce graft size, we have studied the possibility that such propagation may affect stem cell quality. In order to do so, we have assessed the recovery of different stem cell subsets in CD34+ PBSC after a 7-day serum-free liquid culture using CAFC and LTC-CFC assays. A numerical expansion of stem cell subsets was observed in the presence of interleukin-3 (IL-3), stem cell factor, and IL-6, while stroma-contact, stromal soluble factors, or combined addition of FLT3-ligand and thrombopoietin improved this parameter. In contrast, ex vivo culture severely reduced the ability of the graft to produce progenitors in LTC while stromal soluble factors partly abrogated this quality loss. The best conservation of graft quality was observed when the PBSC were cultured in stroma-contact. These data suggest that ex vivo propagation of PBSC may allow numerical expansion of various stem cell subsets, however, at the expense of their quality. In addition, cytokine-driven PBSC cultures require stroma for optimal maintenance of graft quality.

Antigens, CD34↗
PubMed2006

The relationship between stem subsidence and improvement in the radiolucency in polished tapered stems.

We studied the relationship between stem subsidence and improvement in the initial radiolucency at the bone-cement interface in polished- and rough-surface stems. Stem subsidence was seen in 34 of 42 hips (81.0%), and improvement in the initial radiolucency was seen in 15 hips (35.7%) in collarless polished tapered stems at 1 year after operation. In polished stems, stem subsidence in cases with improvement in the initial radiolucency was significantly greater than in those with no change (average 1.12 mm and 0.48 mm, P<0.005). In rough-surface stems partially coated with polymethylmethacrylate (VerSys Cemented Plus), no stem subsidence and no improvement in the initial radiolucency was seen. In polished stems, stem subsidence leads to cement creep and compressive force on the bone-cement interface and can improve the initial radiolucency.

Aged↗
PubMed2004

Unstable versus stable uncemented femoral stems: a radiological study of periprosthetic bone changes in two types of uncemented stems with different concepts of fixation.

INTRODUCTION: Uncemented stems in total hip arthroplasty (THA) are used increasingly often because they are believed to offer a reliable long-term fixation. However, periprosthetic bone remodelling has been a worrying issue. A proximal demineralization has been noted in femurs with well-fixed stems, and it has been explained as by-passing of mechanical forces along the fixed implant (stress-shielding). Aseptic loosening has been a major problem in several uncemented series with earlier designs. The objective for this study was to investigate how the host bone adapts to a loose stem compared with a well-fixed stem after a long time. MATERIALS AND METHODS: An investigation with dual-energy X-ray absorptiometry (DEXA), scintimetry and radiological assessment was carried out in 20 patients 8 years after a THA for arthrosis with two different uncemented stems. Ten patients received a stem coated with polytetrafluoroethylene (Anaform); all prostheses showed migration and were considered unstable. Ten patients received a hydroxyapatite-coated stem (Bi-Metric); no prosthesis migrated. RESULTS: Different remodelling patterns were seen. In the unstable group, the periprosthetic bone mineral density (BMD) was significantly reduced along the entire stem, while in the stable group only proximal bone loss was seen. The scintigraphic uptake was increased under the stem tip in both groups, and among unstable stems uptake was also increased in the calcar region. CONCLUSION: The assessment of periprosthetic bone remodelling after uncemented THA with long-term observation shows a different host-bone response in stable versus unstable femoral implants. Prior to a femoral revision, measurement of the BMD could be beneficial; it may guide the surgeon when deciding which surgical technique to use.

Absorptiometry, Photon↗
PubMed2003

Structure of the intact stem and bulge of HIV-1 Psi-RNA stem-loop SL1.

The Psi-RNA packaging signal of the human immunodeficiency virus type-1 (HIV-1) genome contains a 35 nucleotide stem-loop, termed SL1, which is important for efficient genome packaging during virus assembly and for reverse transcription during infectivity. The predicted secondary structure of SL1 consists of an upper stem with a GC-rich loop that facilitates dimerization, a lower stem, and an intervening bulge (G5, A24-G25-G26) that is both strictly conserved and essential for efficient packaging of the viral genome. The structure of the upper stem in both the kissing and duplex dimer forms have been determined recently. Here, we report the structure of an engineered form of SL1 (SL1(m)) that contains a GAGA tetraloop substituted for the GC-rich loop. This construct does not aggregate and remains monomeric at concentrations up to 1mM, enabling structural studies of the intact stems and bulge. The structure was refined using 1H-13C residual dipolar couplings. The upper stem (C6-G12, C17-G23) is in close agreement with X-ray structures of kissing and duplex dimer forms of related oligoribonucleotides, and nucleotides C1-G4 and C27-G30 form the expected A-helical lower stem. Residues G5 and A24 of the predicted bulge form a G-A mismatch that stacks with the upper stem, and residues G25 and G26 stack between the G-A mismatch and the lower stem in a manner that produces a hole in the center of the bulge and a 25(+/-4) degrees bend between the upper and lower stems. SL1(m) exhibits relatively poor affinity for the HIV-1 nucleocapsid protein, suggesting that the bulge plays other roles in genome packaging.

Base Sequence↗
PubMed2001

The intramolecular stem-loop structure of U6 snRNA can functionally replace the U6atac snRNA stem-loop.

The U6 spliceosomal snRNA forms an intramolecular stem-loop structure during spliceosome assembly that is required for splicing and is proposed to be at or near the catalytic center of the spliceosome. U6atac snRNA, the analog of U6 snRNA used in the U12-dependent splicing of the minor class of spliceosomal introns, contains a similar stem-loop whose structure but not sequence is conserved between humans and plants. To determine if the U6 and U6atac stem-loops are functionally analogous, the stem-loops from human and budding yeast U6 snRNAs were substituted for the U6atac snRNA structure and tested in an in vivo genetic suppression assay. Both chimeric U6/U6atac snRNA constructs were active for splicing in vivo. In contrast, several mutations of the native U6atac stem-loop that either delete putatively unpaired residues or disrupt the putative stem regions were inactive for splicing. Compensatory mutations that are expected to restore base pairing within the stem regions restored splicing activity. However, other mutants that retained base pairing potential were inactive, suggesting that functional groups within the stem regions may contribute to function. These results show that the U6atac snRNA stem-loop structure is required for in vivo splicing within the U12-dependent spliceosome and that its role is likely to be similar to that of the U6 snRNA intramolecular stem-loop.

5' Untranslated Regions↗
PubMed2001

The stem-loop binding protein forms a highly stable and specific complex with the 3' stem-loop of histone mRNAs.

Replication-dependent histone mRNAs end in a highly conserved 26-nt stem-loop structure. The stem-loop binding protein (SLBP), an evolutionarily conserved protein with no known homologs, interacts with the stem-loop in both the nucleus and cytoplasm and mediates nuclear-cytoplasmic transport as well as 3'-end processing of the pre-mRNA by the U7 snRNP. Here, we examined the affinity and specificity of the SLBP-RNA interaction. Nitrocellulose filter-binding experiments showed that the apparent equilibrium dissociation constant (Kd) between purified SLBP and the stem-loop RNA is 1.5 nM. Binding studies with a series of stem-loop variants demonstrated that conserved residues in the stem and loop, as well as the 5' and 3' flanking regions, are required for efficient protein recognition. Deletion analysis showed that 3 nt 5' of the stem and 1 nt 3' of the stem contribute to the binding energy. These data reveal that the high affinity complex between SLBP and the RNA involves sequence-specific contacts to the loop and the top of the stem, as well the base of the stem and its immediate flanking sequences. Together, these results suggest a novel mode of protein-RNA recognition that forms the core of a ribonucleoprotein complex central to the regulation of histone gene expression.

Animals↗
PubMedDate not supplied

Ex vivo expansion of limbal epithelial stem cells: amniotic membrane serving as a stem cell niche.

Identification, maintenance, and expansion of stem cells for subsequent transplantation has become a new strategy for treating many diseases in most medical subspecialties. The stem cells of the corneal epithelium are located in the limbal basal layer and are the ultimate source for constant corneal epithelial renewal. Like those in other tissues, limbal stem cells are supported by a unique stromal microenvironment called the stem cell niche, which consists of certain extracellular matrix components, cell membrane-associated molecules, and cytokine dialogues. Destructive loss of limbal stem cells or dysfunction of their stromal environment renders many corneas with a clinical entity called limbal stem cell deficiency, which is characterized by variable extents of conjunctival ingrowth depending on the severity of limbal damage. A new strategy of treating limbal stem cell deficiency is to transplant a bio-engineered graft by expanding limbal epithelial stem cells ex vivo on amniotic membrane. This review summarizes the published literature data collectively explaining how amniotic membrane is an ideal biological substrate that can help maintain and support the expansion of limbal epithelial stem cells.

Amnion↗
PubMed2003

Fetal human hematopoietic stem cells can differentiate sequentially into neural stem cells and then astrocytes in vitro.

In some rodent models, there is evidence that hematopoietic stem cells (HSC) can differentiate into neural cells. However, it is not known whether humans share this potential, and, if so, what conditions are sufficient for this transdifferentiation to occur. We addressed this question by assessing the ability of fetal human liver CD34(+)/CD133(+)/CD3(-) hematopoietic stem cells to generate neural cells and astrocytes in culture. We cultured fetal liver-derived hematopoietic stem cells in human astrocyte culture-conditioned medium or using a method wherein growing human astrocytes were separated from cultured, nonadherent hematopoietic stem cells by a semipermeable membrane in a double-chamber co-culture system. Hematopoietic stem cell cultures were probed for neural progenitor cell marker expression (nestin and bone morphogenic protein-2 [BMP-2]) during growth in both culture conditions. RT-PCR, western blotting, and immunocytochemistry assays showed that cells cultured in either condition expressed nestin mRNA and protein and BMP-2 mRNA. HSC similarly cultured in nonconditioned medium or in the absence of astrocytes did not express either marker. Cells expressing these neural markers were transferred and cultured on poly-D-lysine-coated dishes with nonconditioned growth medium for further study. Immunocytochemistry demonstrated that these cells differentiated into astrocytes after 8 days in culture as indicated by their morphology and expression of the astrocytic markers glial fibrillary acidic protein (GFAP) and S100, as well as by their rate of proliferation, which was identical to that of freshly isolated fetal brain astrocytes. These findings demonstrate that neural precursor gene expression can be induced when human hematopoietic stem cells are exposed to a suitable microenvironment. Furthermore, the neural stem cells generated in this environment can then differentiate into astrocytes. Therefore, human hematopoietic stem cells may be an alternative resource for generation of neural stem cells for therapy of central nervous system defects resulting from disease or trauma.

AC133 Antigen↗
PubMed2006

A natural stem cell therapy? How novel findings and biotechnology clarify the ethics of stem cell research.

The natural replacement of damaged cells by stem cells occurs actively and often in adult tissues, especially rapidly dividing cells such as blood cells. An exciting case in Boston, however, posits a kind of natural stem cell therapy provided to a mother by her fetus-long after the fetus is born. Because there is a profound lack of medical intervention, this therapy seems natural enough and is unlikely to be morally suspect. Nevertheless, we feel morally uncertain when we consider giving this type of therapy to patients who would not naturally receive it. Much has been written about the ethics of stem cell research and therapy; this paper will focus on how recent advances in biotechnology and biological understandings of development narrow the debate. Here, the author briefly reviews current stem cell research practices, revisits the natural stem cell therapy case for moral evaluation, and ultimately demonstrates the importance of permissible stem cell research and therapy, even absent an agreement about the definition of when embryonic life begins. Although one promising technology, blighted ovum utilisation, uses fertilised but developmentally bankrupt eggs, it is argued that utilisation of unfertilised eggs to derive totipotent stem cells obviates the moral debate over when life begins. There are two existing technologies that fulfil this criterion: somatic cell nuclear transfer and parthenogenic stem cell derivation. Although these technologies are far from therapeutic, concerns over the morality of embryonic stem cell derivation should not hinder their advancement.

Adult↗
PubMed1996

Individual stem cell quality in leukapheresis products is related to the number of mobilized stem cells.

Peripheral blood stem cells (PBSC) are used for stem cell support in patients after intensive chemotherapy and generally permit faster hematopoietic recovery than bone marrow. The development of different protocols for chemotherapy conditioning, mobilization, and ex vivo manipulation of PBSC may potentially lead to loss of primitive hematopoietic stem cells or reduction of their quality. To characterize the frequency of different stem cell subsets and their quality per mobilized PBSC, we have studied 47 leukapheresis products (LPs) of 21 cancer patients using stroma-dependent long-term culture (LTC) and limiting dilution-type cobblestone area forming cell (CAFC) assays. A large variation in CAFC week-type frequencies between the LPs was observed. The frequencies of CAFC week 2 as a tentative indicator of progenitor cells and transiently repopulating hematopoietic stem cells ranged from 0.89 to 205 per 10(5) mobilized nucleated cells and the frequencies of more primitive CAFC week 6 varied between 0.37 and 48. The average total colony-forming cell (CFC) production per CAFC at week 6 varied between 1.2 and 730, as determined in parallel LTC. In contrast to LPs, bone marrow samples generated 4.2 to 48 CFC per CAFC at week 6. Notably, a poor stem cell quality was consistently found in LPs that contained less than 5,000 CAFC week 6 per kilogram of body weight. Frequency analyses of CFCs, CAFC subtypes, and immunophenotypic subsets showed a good level of mutual correlation, suggesting identical mobilization kinetics of different stem cell subsets. The premobilization chemotherapy intensity was directly correlated with both decreasing frequency and quality of the CAFC week 6 in LPs. The frequency of CFCs, immunophenotypic subsets, and CAFC subsets transplanted and the transplant quality as determined in LTC assays was related to the neutrophil and platelet recovery time after PBSC transplantation. Although the number of progenitor cells transplanted and the in vitro transplant quality showed the best correlation with early hematopoietic recovery, the data did not permit determination of which stem cell subsets are predominantly responsible for early posttransplantation recovery. As a result, frequency and quality analysis of stem cell subsets may be a useful tool to monitor and calibrate the efficacy of novel mobilization regimens and ex vivo manipulation of PBSC.

Adult↗
PubMed2005

Incorporating protein transduction domains (PTD) within intracellular proteins associated with the 'stemness' phenotype. Novel use of such recombinant 'fusion' proteins to overcome current limitations of applying autologous adult stem cells in regenerative medicine?

Adult stem cells originating from post-natal tissues hold tremendous promise in regenerative medicine. Nevertheless, there are several deficiencies of adult stem cells that would limit their application in transplantation therapy, in particular their relative scarcity, restricted multi-potency and limited proliferative capacity in vitro. A possible approach to overcome these limitations would be to genetically modulate adult stem cells to strongly express genes that are closely associated with the 'stemness' phenotype. Overwhelming safety concerns would preclude the direct application of recombinant DNA technology in genetic modulation. Moreover, constitutive expression of 'stemness' genes would prevent adult stem cells from participating in tissue/organ regeneration upon transplantation. A novel alternative would be to incorporate protein transduction domains within intracellular proteins (i.e. transcription factors) that are associated with the 'stemness' phenotype. Such recombinant fusion proteins would then have the ability to translocate across the cell membrane and be internalized within the cytosol, thereby enabling them to exert a gene-modulatory effect on the cell, without any permanent genetic alteration. This would be particularly useful for maintaining the 'stemness' of adult stem cell populations during extensive ex vivo proliferation, to generate adequate cell numbers for transplantation therapy.

Adult↗