Proliferative potential of impacted tooth lesions using Ki67 labelling index-A clinicopathological insight.

Tooth impaction is a frequent phenomenon, and the prevalence and distribution of this entity in different regions of the jaws may vary considerably. The third molars, maxillary canines, maxillary and mandibular premolars, and maxillary central incisors are the most commonly affected teeth. Impacted teeth in children and adolescents are rarely associated with pathological changes, but the prevalence of problems has been found to increase in later decades. Impacted teeth are commonly asymptomatic and not associated with any pathologic lesions for years. Proliferative potential of various odontogenic lesions were calculated using Ki-67 labeling index calculation, with the highest index of Unicystic Ameloblastoma followed by Adenomatoid odontogenic tumor, Unicystic Ameloblastoma, followed by the dental follicle. Ki-67 is a marker of cell proliferation, used as an important diagnostic marker in the pathologic differentiation of various lesions. It is always better to orthodontically treat or extract asymptomatic impacted teeth to avoid or to restrict the proliferative capacity of the dental follicle. Treatment decisions about the third molar have important clinical and cost implications.

Novel Immortalized Human Multipotent Mesenchymal Stromal Cell Line for Studying Hormonal Signaling.

Multipotent mesenchymal stromal cells (MSCs) integrate hormone and neuromediator signaling to coordinate tissue homeostasis, tissue renewal and regeneration. To facilitate the investigation of MSC biology, stable immortalized cell lines are created (e.g., commercially available ASC52telo). However, the ASC52telo cell line has an impaired adipogenic ability and a depressed response to hormones, including 5-HT, GABA, glutamate, noradrenaline, PTH and insulin compared to primary cells. This markedly reduces the potential of the ASC52telo cell line in studying the mechanisms of hormonal control of MSC's physiology. Here, we have established a novel immortalized culture of adipose tissue-derived MSCs via forced telomerase expression after lentiviral transduction. These immortalized cell cultures demonstrate high proliferative potential (up to 40 passages), delayed senescence, as well as preserved primary culture-like functional activity (sensitivity to hormones, ability to hormonal sensitization and differentiation) and immunophenotype up to 17-26 passages. Meanwhile, primary adipose tissue-derived MSCs usually irreversibly lose their properties by 8-10 passages. Observed characteristics of reported immortalized human MSC cultures make them a feasible model for studying molecular mechanisms, which regulate the functional activities of these cells, especially when primary cultures or commercially available cell lines are not appropriate.

Quantitative Evaluation of Proliferative Potential Using Flow Cytometry Reveals Intratumoral Heterogeneity and Its Relevance to Tumor Characteristics in Vestibular Schwannomas.

This study sought to explore the existence and clinical significance of intratumoral heterogeneity of proliferative potential in vestibular schwannoma (VS). Rapid intraoperative flow cytometry was utilized with raw samples to measure the proliferative ability of VS. The proliferation index (PI) was defined as the ratio of the number of cells with greater than normal DNA content to the total number of cells. A total of 66 specimens (26 from the intrameatal portion and 40 from the cisternal portion) were obtained from 34 patients with VS. There was a moderate correlation between the PI and MIB-1 labelling index values (R = 0.57, p < 0.0001). In contrast, the patterns of heterogeneity, represented by the proportion of intrameatal PI to cisternal PI, were associated with tumor size (p = 0.03). In addition, preoperative hearing tended to be poor in cases where the intrameatal PI was higher than the cisternal PI (p = 0.06). Our data demonstrated the presence of intratumoral heterogeneity of proliferative potential in VS and its relationship with tumor characteristics. The results of this study may advocate the resection of the intrameatal portion of large VSs treated with planned subtotal resection, especially in cases of poor preoperative hearing function.

Subpopulation Heterogeneity of NK Cells during the Genetic Modification for Subsequent Use in Targeted Therapy.

Obtaining genetically engineered NK cells is a developing area of immunotherapy. In this work, we analyzed the subset heterogeneity of NK cells subjected to retroviral transduction, taking into account the content of adaptive NK cell progenitors. It was shown that subsets KIR2DL2/DL3+, as well as CD57-KIR2DL2/DL3+NKG2C+, can be modified with greater efficiency than the corresponding subsets that do not carry the KIR2DL2/DL3 and NKG2C markers. After genetic modification, the CD57-KIR2DL2/DL3+NKG2C+ cells began to express CD57 de novo, acquiring the adaptive NK cell phenotype.

Phytochemical profiling of Azima tetracantha Lam. leaf methanol extract and elucidation of its potential as a chain-breaking antioxidant, anti-inflammatory and anti-proliferative agent.

Azima tetracantha, a traditional medicinal plant included in the order Brassicales and family Salvadoraceae, is widely used as a dietary supplement in folklore medicines. The plant is also used for the treatment of rheumatism, diarrhea and other inflammatory disorders. The present investigation focused on the phytochemical composition, radical scavenging, reducing potential and anti-proliferative activities of the A. tetracantha leaves. Quantitative estimation of the polyphenols and flavonoids revealed significantly elevated levels in the methanol extract. Corroborating with this, methanol extract exhibited higher in vitro anti-radical scavenging effect against 2,2-diphenyl-1- picrylhydrazyl (34.14 ± 2.19 µg/mL), and hydrogen peroxide (44.96 ± 1.77 µg/mL), as well as ferric reducing properties (58.24 ± 6.98 µg/mL). The methanolic extract also showed strong lipoxygenase (71.42 ± 6.36 µg/mL) and nitric oxide inhibitory activities (94.23 ± 8.11 µg/mL). Cytotoxic activity against MCF7 cells was found to be higher (IC50= 37.62 ± 2.94 µg/mL), than that of MDAMB231 cells (IC50= 69.11 ± 5.02 µg/mL). The qPCR-based analysis indicated dose-dependent increase in the expression of the pro-apoptotic genes such as executioner caspases and apoptotic protease activating factor-1. Overall, the results indicated the possible use of methanol extract of A. tetracantha leaves as a chain-breaking antioxidant molecule and are capable of inhibiting inflammatory enzymes and the proliferative potential of breast cancer cells.

Decrease of Proliferative Potential and Vascular Density of Giant Prolactinoma in Patients Treated with Cabergoline.

INTRODUCTION: Currently, cabergoline therapy is the main treatment for prolactinomas. The use of the drug in most cases leads to regression of the tumor, normalization of prolactin (PRL) levels, and restoration of gonadotropic function. The mechanism of its action in tumor cells "in vivo" tracked in dynamics in the same human tumor is of considerable interest. MATERIALS AND METHODS: A 30-year-old male was admitted to N.N. Burdenko National Medical Research Center of Neurosurgery. An magnetic resonance imaging (MRI) revealed a giant pituitary adenoma. The level of PRL was more than 5000 mU/l (30-360) (serum dilution was not used to determine PRL). Transcranial microsurgical removal of the tumor was performed. He was treated by cabergoline after surgery. Endoscopic transsphenoidal approach was repeated with subtotal removal of the rest of the tumor. Morphological and immunohistochemical studies of the tumor were done. RESULTS: A morphological study revealed PRL-positive tumor with a Ki-67 LI of 8% with a distinctive expression of D2R, CD31, and CD34 markers. Control MRI in 3 months after surgery revealed remnants of a tumor of endoinfrasellar localization, the tumor remainders were found in endoinfrasellar localization. The tumor retained pronounced immunopositivity to PRL and D2R and a decrease in the Ki-67 to 2% and in the expression of CD31 and CD34. Subsequent therapy with cabergoline resulted in persistent normoprolactinemia, restoration of androgenic function, and absence of tumor recurrence during the 10-year follow-up period. CONCLUSIONS: Cabergoline is an effective treatment for prolactinoma, which leads to tumor regression. One of its mechanisms is the reduction of the proliferative index and tumor angiogenesis.

Gene expression markers in horse articular chondrocytes: Chondrogenic differentiaton IN VITRO depends on the proliferative potential and ageing. Implication for tissue engineering of cartilage.

Chondrocyte dedifferentiation is a key limitation in therapies based on autologous chondrocyte implantation for cartilage repair. Articular chondrocytes, obtained from (metacarpophalangeal and metatarsophalangeal) joints of different aged horses, were cultured in monolayer for several passages (P0 to P8). Cumulative Populations Doublings Levels (PDL) and gene expression of relevant chondrocyte phenotypic markers were analysed during culturing. Overall data confirmed that, during proliferation in vitro, horse chondrocytes undergo marked morphological and phenotypic alterations of their differentiation status. Particularly, the dedifferentiation started early in culture (P0-P1) and was very marked at P3 subculture (PDL 4-6): proliferative phase after P3 could be critical for maintenance/loss of differentiation potential. In elderly animals, chondrocytes showed aspects of dedifferentiation shortly after their isolation, associated with reduced proliferative capacity. Regarding the gene expression of major cartilage markers (Col2, Aggrecan, SOX9) there was a very early reduction (P1) in proliferating chondrocytes independent of age. The chondrocytes from adult donors showed a more stable expression (up to P3) of some (Col6, Fibromodulin, SOX6, TGß1) markers of mature cartilage; these markers could be tested as parameter to determine the dedifferentiation level. This study can provide parameters to identify up to which "culture step" chondrocytes for implantation with a conserved phenotypic potential can be obtained, and to test the efficiency of biomaterial scaffold or chondroinductive media/signals to maintain/recover the chondrocyte phenotype. Moreover, the determination of levels and time related expression of these markers can be useful during the chondroinduction of mesenchymal stem cells.

TCEA1 regulates the proliferative potential of mouse myeloid cells.

Leukemia is a malignance with complex pathogenesis and poor prognosis. Discovery of noval regulators amenable to leukemia could be of value to gain insight into the pathogenesis, diagnosis and prognosis of leukemia. Here, we conducted a large-scale shRNA library screening for functional regulators in the development of myeloid cells in primary cells. We identified eighteen candidate regulators in the primary screening. Those genes cover a wide range of cellular functions, including gene expression regulation, intracellular signaling transduction, nucleotide excision repair, cell cycle control and transcription regulation. In both primary screening and validation, shRNAs targeting Tcea1, encoding the transcription elongation factor A (SII) 1, exhibited the greatest influence on the proliferative potential of cells. Knocking down the expression of Tcea1 in the 32Dcl3 myeloid cell line led to enhanced proliferation of myeloid cells and blockage of myeloid differentiation induced by G-CSF. In addition, silence of Tcea1 inhibited apoptosis of myeloid cells. Thus, Tcea1 was identified as a gene which can influence the proliferative potential, survival and differentiation of myeloid cells. These findings have implications for how transcriptional elongation influences myeloid cell development and leukemic transformation.

Low dose ionizing irradiation suppresses cellular senescence in normal human fibroblasts.

PURPOSE: Exposure to high dose ionizing radiation leads to premature cell senescence and suppression of cell proliferation. In contrast, low dose and low dose-rate gamma-irradiation can lead to stimulation of cell proliferation. We aimed to examine whether the low dose radiation-induced proliferation of normal human fibroblasts can lead to a progressive depletion of proliferation potential and to an early onset of senescence. MATERIALS AND METHODS: Normal human embryonic lung fibroblasts (HELF-104) at passage 22-24 were gamma-irradiated with doses of 0 (sham-irradiation), 10, 30, 50, 90, 120, 150, 200, and 500 mGy as well as 1 and 2 Gy. After irradiation, the fraction of cells positively stained for senescence-associated ß-galactosidase activity was measured weekly until the cell culture completely ceased to proliferate. RESULTS: We show that single irradiation of HELF-104 cells with 30 and 50 mGy resulted in deceleration of senescence. The suppression of senescence was observed during almost the entire length of the study up to a complete arrest of cell growth. CONCLUSIONS: Our data, together with the previously published observation of delayed stimulation of proliferation in HELF-104 cells exposed to 30 mGy, suggest that low dose gamma-irradiation can increase the overall proliferative potential of normal human fibroblasts.

The effect of the deuterium depleted water on the biological activity of the eukaryotic cells.

Here we show the dependence of the unicellular biosensor S.ambigua lifespan on the water D/H isotopic composition. This dependence is bell-shaped with descents both in case of deficiency or excess of deuterium in water. The influence of the water D/H isotopic composition on the cell culture proliferative potential and colony forming efficiency in vitro was tested on the human dermal fibroblasts. We observed that the deuterium depleted water stimulates cell colony formation at the early passages. The dynamics of the cell doubling index in the deuterium depleted water-based growth medium showed higher proliferation potential compared to the water with normal isotopic composition. Using scratch assay, we have also studied the impact of the growth medium D/H isotopic composition on the cell motility of human cancer cell lines A549 and HT29. We have shown that the deuterium depleted water considerably suppressed cancer cell lines amoeboid movement in vitro.

Isolation and characterization of human umbilical cord-derived endothelial colony-forming cells.

Endothelial colony-forming cells (ECFCs) are a population of endothelial progenitor cells (EPCs) that display robust proliferative potential and vessel-forming capability. Previous studies have demonstrated that a limited number of ECFCs may be obtained from adult bone marrow, peripheral blood and umbilical cord (UC) blood. The present study describes an effective method for isolating ECFCs from human UC. The ECFCs derived from human UC displayed the full properties of EPCs. Analysis of the growth kinetics, cell cycle and colony-forming ability of the isolated human UC-ECFCs indicated that the cells demonstrated properties of stem cells, including relative stability and rapid proliferation in vitro. Gene expression of Fms related tyrosine kinase 1, kinase insert domain receptor, vascular endothelial cadherin, cluster of differentiation (CD)31, CD34, epidermal growth factor homology domains-2, von Willebrand factor and endothelial nitric oxide synthase was assessed by reverse transcription-polymerase chain reaction. The cells were positive for CD34, CD31, CD73, CD105 and vascular endothelial growth factor receptor-2, and negative for CD45, CD90 and human leukocyte antigen-antigen D related protein according to flow cytometry. 1,1'-dioctadecyl-3,3,3',3'-tetra-methyl-indocarbocyanine perchlorate-labeled acetylated low-density lipoprotein and fluorescein isothiocyanate-Ulex europaeus-l were used to verify the identity of the UC-ECFCs. Matrigel was used to investigate tube formation capability. The results demonstrated that the reported technique is a valuable method for isolating human UC-ECFCs, which have potential for use in vascular regeneration.

Physicochemical Properties, Antioxidant and Anti-proliferative Capacities of Dried Leaf and Its Extract from Xao tam phan (Paramignya trimera).

Xao tam phan (Paramignya trimera) has been used for the treatment of cancer and cancer-like aliments. Among different parts of the P. trimera plant, leaf is considered as a residual part after harvesting of the root. This study aimed to determine the physiochemical properties and the antioxidant and anti-proliferative capacities of P. trimera leaf (PTL) using microwave drying for the preparation of dry sample; MeOH and microwave-assisted extraction for the preparation of crude extract; and freeze-drying for the preparation of powdered extract. The results showed that total phenolic, total flavonoid, proanthocyanidin, and saponin contents of PTL prepared by microwave drying at 450 W were 25.4 mg gallic acid equiv. (GAE), 86.3 mg rutin equiv. (RE), 5.6 mg catechin equiv. (CE), and 702.1 mg escin equiv. (EE) per gram dried sample, respectively. Gallic acid, protocatechuic acid, ellagic acid, rutin, and quercetin were identified in the PTL MeOH extract. Dried PTL displayed potent antioxidant activity, while the powdered PTL extract exhibited great anti-proliferative capacity on various cancer cell lines including MiaPaCa-2 (pancreas), HT29 (colon), A2780 (ovarian), H460 (lung), A431 (skin), Du145 (prostate), BE2-C (neuroblastoma), MCF-7 (breast), MCF-10A (normal breast), and U87, SJ-G2, and SMA (glioblastoma). Anti-proliferative capacity on pancreatic cancer cells (MiaCaPa2, BxPc3, and CFPAC1) of PTL extract (200 µg/ml) was significantly higher (P < 0.05) than those of ostruthin (20 µg/ml) and gemcitabine (50 nm), and to be comparable to the powdered P. trimera root extract and a saponin-enriched extract from quillajia bark (a commercial product). The findings from this study allow us to conclude that the PTL is a rich source of phytochemicals that possess promising antioxidant and anti-proliferative activities, therefore it shows potential as lead compounds for application in the nutraceutical, medicinal and pharmaceutical industries.

Potency testing of mesenchymal stromal cell growth expanded in human platelet lysate from different human tissues.

BACKGROUND: Mesenchymal stromal cells (MSCs) have been largely investigated, in the past decade, as potential therapeutic strategies for various acute and chronic pathological conditions. MSCs isolated from different sources, such as bone marrow (BM), umbilical cord tissue (UCT) and adipose tissue (AT), share many biological features, although they may show some differences on cumulative yield, proliferative ability and differentiation potential. The standardization of MSCs growth and their functional amplification is a mandatory objective of cell therapies. The aim of this study was to evaluate the cumulative yield and the ex vivo amplification potential of MSCs obtained from various sources and different subjects, using defined culture conditions with a standardized platelet lysate (PL) as growth stimulus. METHODS: MSCs isolated from BM, UCT and AT and expanded in human PL were compared in terms of cumulative yield and growth potential per gram of starting tissue. MSCs morphology, phenotype, differentiation potential, and immunomodulatory properties were also investigated to evaluate their biological characteristics. RESULTS: The use of standardized PL-based culture conditions resulted in a very low variability of MSC growth. Our data showed that AT has the greater capacity to generate MSC per gram of initial tissue, compared to BM and UCT. However, UCT-MSCs replicated faster than AT-MSCs and BM-MSCs, revealing a greater proliferation capacity of this source irrespective of its lower MSC yield. All MSCs exhibited the typical MSC phenotype and the ability to differentiate into all mesodermal lineages, while BM-MSCs showed the most prominent immunosuppressive effect in vitro. CONCLUSIONS: The adoption of standardized culture conditions may help researchers and clinicians to reveal particular characteristics and inter-individual variability of MSCs sourced from different tissues. These data will be beneficial to set the standards for tissue collection and MSCs clinical-scale expansion both for cell banking and for cell-based therapy settings.

High proliferative potential endothelial colony-forming cells contribute to hypoxia-induced pulmonary artery vasa vasorum neovascularization.

Angiogenic expansion of the vasa vasorum (VV) is an important contributor to pulmonary vascular remodeling in the pathogenesis of pulmonary hypertension (PH). High proliferative potential endothelial progenitor-like cells have been described in vascular remodeling and angiogenesis in both systemic and pulmonary circulations. However, their role in hypoxia-induced pulmonary artery (PA) VV expansion in PH is not known. We hypothesized that profound PA VV neovascularization observed in a neonatal calf model of hypoxia-induced PH is due to increased numbers of subsets of high proliferative cells within the PA adventitial VV endothelial cells (VVEC). Using a single cell clonogenic assay, we found that high proliferative potential colony-forming cells (HPP-CFC) comprise a markedly higher percentage in VVEC populations isolated from the PA of hypoxic (VVEC-Hx) compared with control (VVEC-Co) calves. VVEC-Hx populations that comprised higher numbers of HPP-CFC also demonstrated markedly higher expression levels of CD31, CD105, and c-kit than VVEC-Co. In addition, significantly higher expression of CD31, CD105, and c-kit was observed in HPP-CFC vs. the VVEC of the control but not of hypoxic animals. HPP-CFC exhibited migratory and tube formation capabilities, two important attributes of angiogenic phenotype. Furthermore, HPP-CFC-Co and some HPP-CFC-Hx exhibited elevated telomerase activity, consistent with their high replicative potential, whereas a number of HPP-CFC-Hx exhibited impaired telomerase activity, suggestive of their senescence state. In conclusion, our data suggest that hypoxia-induced VV expansion involves an emergence of HPP-CFC populations of a distinct phenotype with increased angiogenic capabilities. These cells may serve as a potential target for regulating VVEC neovascularization.

Analysis of the proliferative potential of odontogenic epithelial cells of pericoronal follicles.

AIM: To evaluate the proliferative potential and the cell proliferation rate of odontogenic epithelial cells. MATERIALS AND METHODS: Forty-two cases of pericoronal follicles of impacted third molars were submitted to silver impregnation technique for quantification of argyrophilic nucleolar organizer regions (AgNOR) and immunohistochemical staining for EGFR and Ki-67. For AgNOR quantification, the mean number of active nucleolar organizer regions per nucleus (mAgNOR) and the percentage of cells with 1, 2, 3 and 4 or more AgNORs per nucleus (pAgNOR) were quantified. Ki-67 immunolabeling was quantified, whereas for EGFR, a descriptive analysis of staining patterns (membrane, cytoplasm or membrane + cytoplasm positivity) was performed. We evaluated the reduced epithelium of the enamel organ and/or islands of odontogenic epithelium present in the entire connective tissue. RESULTS: mAgNOR were 1.43 (1.0-2.42) and were significantly different among pericoronary follicles from upper and lower teeth (p = 0.041). Immunostaining of Ki-67 was negative in all cases. EGFR immunolabeling was found mainly in the cytoplasm and was more intense in islands and cords when compared to reduced epithelium of the enamel organ. CONCLUSION: Odontogenic epithelial cells of some pericoronal follicles have proliferative potential, suggesting their association with the development of odontogenic lesions. CLINICAL SIGNIFICANCE: The authors suggest that nonerupted, especially of the lower teeth, should be monitored and if necessary removed.

The Germinative Epithelium of Sheep Vibrissae and Wool Follicles has Extensive Proliferative Potential but is Dependent on the Dermal Papilla.

AIM: To investigate the growth potential of keratinocytes derived from the germinative epithelium (GE) of ovine hair follicles. Stem cells from the outer root sheath (ORS) of hair follicles migrate to the GE in the lower follicle where they proliferate and differentiate to form the hair fiber. It has been suggested that the GE comprises transit-amplifying cells and that the duration of anagen is determined by their limited proliferative potential. However, we show here that keratinocytes derived from the GE of ovine follicles grow extensively in vitro, arguing against this hypothesis. MATERIALS AND METHODS: Primary cultures of keratinocytes were initiated from microdissected GE tissue from ovine vibrissae and wool follicles. Clonal lines of keratinocytes were derived by limiting dilution. Their growth potential was determined by exhaustive serial passaging. Expression of differentiation markers was evaluated by real-time polymerase chain reaction. RESULTS: Initiation of these cultures required that interaction between the GE and dermal papilla was maintained. However, the keratinocytes could subsequently be cloned and were grown as pure cell populations for 26-52 cell doublings. This proliferative potential is several orders of magnitude greater than required to maintain a single anagen phase. The keratinocytes were indistinguishable from ORS keratinocytes from the same follicles, expressing K14 while undifferentiated, and upregulating the epidermal and inner root sheath markers, loricrin and KRT27 on differentiation. Thus, these cells initially depend on papilla-derived signals to grow, but can revert to an ORS-like phenotype in vitro. Their extensive proliferative capacity shows that the GE is not an exclusively transit-amplifying cell population.

Effects of preservation time on proliferative potential of human limbal stem/progenitor cells.

AIM: To determine the proliferative potential and the maintenance of stem cell activity in stored human limbal tissues, and correlate this with the preservation time, cell viability and the expression of stem cell markers. METHODS: Thirty limbal rims were split into 4 parts and stored in corneal preservation medium at 4°C for 0, 1, 4, or 7 days. The limbal stem cell and mitotic markers P63, CK19, proliferating cell nuclear antigen (PCNA), and Ki67 were determined by immunohistochemical staining. The proliferative potential of limbal epithelial cells was assessed by cell viability, the ability of generating stratified epithelium, and colony forming assay. RESULTS: The stored tissues maintained limbal stratified structure to 7 days and exhibited comparable expression level of stem cell and mitotic markers. The proportion of viable cells decreased with the prolonged preservation time, while colony forming efficiency decreased from the 1(st) day and disappeared at the 4(th) day. When inoculated on amniotic membrane, the cells preserved for 1 day formed a stratified epithelium, while the cells from 4 days' preservation formed a discontinuous layer. CONCLUSION: The colony forming efficiency of limbal epithelial stem/progenitor cells decreased rapidly with the increasing preservation time, while the expression level of markers and capacity of forming epithelial monolayer on amniotic membrane decreased gradually. The limbal epithelial stem cells lost their function earlier than the lost expression level of stem cell markers. This may help us to better choose the appropriate preservation grafts for future limbal stem cell transplantation.

Age-related Deterioration of Hematopoietic Stem Cells.

Aging is the process of system deterioration over time in the whole body. Stem cells are self-renewing and therefore have been considered exempt from the aging process. Earlier studies by Hayflick showed that there is an intrinsic limit to the number of divisions that mammalian somatic cells can undergo, and cycling kinetics and ontogeny-related studies strongly suggest that even the most primitive stem cell functions exhibit a certain degree of aging. Despite these findings, studies on the effects of aging on stem cell functions are inconclusive. Here we review the age-related properties of hematopoietic stem cells in terms of intrinsic and extrinsic alterations, proliferative potential, signaling molecules, telomere and telomerase, senescence and cancer issues, regenerative potential and other indications of stem cell aging are discussed in detail.