In the May 20th early edition of PNAS, M. V. Plikus et al. from the University of Southern California School of Medicine published their study results on the role of the circadian clock in regenerating hair follicles. The investigators identified two key sites (epithelial matrix and mesenchymal dermal papilla) where peripheral circadian clock activity influence daily mitotic rhythm of anagen hair follicles. In the epithelial matrix, the circadian clock influence of mitotic rhythmicity was attributed to hair growing faster in the morning than in the evening. Sensitivity to genotoxic stress was found to be time-of-day dependent such as susceptibility to DNA damage during mitosis. In mice, the researchers found that g-radiation induce dramatic hair loss in the morning, during peak mitosis, compared to minimal loss following radiation exposure in the evening. Additionally, the experimental data revealed that the diurnal radio-protective effect of the circadian clock was lost in circadian mutants where hair follicles undergo asynchronous mitosis. It was further demonstrated that circadian clock activity "coordinates cell cycle progression with genotoxic stress responses by synchronizing Cdc2/Cyclin B-mediated G2/M checkpoint."
In the May 13th online early edition of PNAS, P. Wu et al. from University of Southern California published their study results on tooth renewal in alligators. The authors noted that alligators have well-organized teeth similar to mammals and can undergo life-long renewal. The investigators used multiple mitotic labeling to map stem cells to the enlarged bulge of the dental lamina which contains quiescent odontogenic progenitors. Activation of the progenitors and initiation of the tooth cycle correlates upregulation of the b-catenin signaling pathway and disappearance in the bulge of soluble frizzled-related protein 1. The researchers also found "that the dermal niche adjacent to the dermal lamina dynamically expresses neural cell adhesion molecule, tenascin-C, and other molecules. The authors further noted that "in development, asymmetric b-catenin localization leads to the formation of a heterochronous and complex tooth family unit configuration."
M. Sundberg et al. from Harvard Medical School reported in the May 10th online early publication of Stem Cells their study results on comparing the difference in safety and efficacy between dopaminergic neurons (DA) neurons derived from both human embryonic and induced pluripotent stem cells (iPSCs) and non-human iPSCs. With fluorescence-activated cell storting (FACS), the investigators enriched for a population of dopaminergic neurons having a NCAM+/CD29low phenotype. The sorted NCAM+/CD29low DA neurons differentiated from iPSCs were positive for FOXA2/TH and EN1/TH as well as having increased expression levels of FOXA2, LMX1A, TH, GIRK2,PITX3, EN1, NURR1 mRNA compared to unsorted neural cell populations. The experimental results revealed that non-primate iPSC-derived NCAM+/CD29low DA neurons restored motor in Parkinsonian rat model (6-OHDA lesioned rats) 16 weeks after implantation. Additionally, transplanted sorted cells were found to integrate into striatium of the rodent brain. One year survival of autologous transplantation of primate iPSC-derived (FOXA2/TH positive) neurons was observed in the striatum of 1/2 primate without immunosuppression.
In the March 27th issue of BioMacromolecules, N. Singh et al. from the University of Bristol (U.K.) reported their study results on using a blend of cellulose and silk to form scaffolds which can induce mesenchymal stem cells to support human mesenchymal stem cells (MSCs) growth and induce chondrogenic differentiation. In order to reduce cellulose stiffness, the investigators used ionic liquid solvents for blending cellulose with silk. A 75:25 ratio of cellulose to silk resulted in a significant upregulation of chondrogenic marker Sox9, aggregan , and type II collagen in the absence of growth factors. No effect was reported when MSCs were seeded onto either neat cellulose or a 50:50 blend of cellulose to silk. Additionally, the study data revealed that the chondrogenic blend of cellulose did not induce adipogenesis or osteogenesis. The authors concluded that their study results suggest that the 75:25 cellulose to silk ratio was specific for "stem cell differentiation into chrondrogenic lineage without addition of the soluble growth factor TGF-b."
In the January issue of Experimental Biology and Medicine, B.-W. Qi et al. from Zhongnan Hospital of Wuhan University (China) reported their study results in determining whether rabbit bone marrow-derived mesenchynmal stem cells (BMSCs) transfected human transforming growth factor-b1 (hTGF-b1) in a hydrogel enhanced regeneration of articular cartilage in rabbits. After 16 weeks, the investigators observed that the transfected BMSC (Ad-hTGF-b1) in the thermosensitive hydrogel scaffold appeared to heal the articular defect back to its normal morphological and functional state compared to grafts with either transfected with BMSCs alone, or untreated BMSCs and hydrogel. Immunohistochemical staining of type II collagen showed transfected BMSCs combined with a hydrogel scaffold had the strongest expression of the type II collagen concomitant with the morphology of the repaired cartilage-comparable to normal cartilage tissue. The tissue healing/repair of the articular cartilage defect was less robust in animals of the other experimental groups. The authors concluded from their study observations that "a thermosensitive and injectable scaffold material, CS/PVA gel engineered with BMSCs transfected with hTGF -b1 can effectively repair rabbit articular cartilage defects."
In the April 17th online early edition of Stem Cells, J. Jung et al. from CHA University (Seoul) published their study results on the role of mesenchymal stem cells (MSCs) in triggering autophagy during tissue repair and regeneration. The investigators used carbon tetrachloride (CCl4) to induce liver injury in rats transplanted with chorionic plate-derived mesenchymal stem cells (CP-MSCs) from the placenta. With markers for apoptosis, autophagy, and cell survival, the experimental results revealed a decrease in caspase activity and an upregulation of factors expressing autophagy, cell survival and regeneration following CP-MSC transplantation. A decrease in necrotic cells and an increase in autophagic signaling were observed in co-cultures experiments using CP-MSCs and CCl4-treated rat primary hepatocytes. The researchers also observed an upregulation in hypoxia inducible factor-1a (HIF-1a) concomitant with regeneration of damaged hepatic cells. HIF-1a was found to promote autophagy by increasing the level LC3 II. The authors concluded from their study results "that the administration of CP-MSCs promotes repair by systemically concomitant mechanisms involving HIF-1a and autophagy."
In the April 2nd online early publication of Cell Transplantation, A. Bhansail et al. from the Post Graduate Institute of Medical Education and Research (Chandigarh, India) published their 21 patient clinical trial results on Phase I/II randomized, single blinded placebo-controlled study with autologous bone marrow-derived stem cell (BMSC) transplantation in patients with Type 2 diabete mellitus (T2DM). Patients in the test group who receive the BMSC initially had their bone marrow aspirated followed by a subsequently infusion of Ficoll-Hypaque separated CD34+and CD45+ mononuclear cells. Twelve weeks after the initial infusion the BMSCs into the "superior pancreatico-duodenal artery, a second dose of BMSCs were administered through ante-cubital vein after mobilization with G-CSF." The primary clinical end point was a 50% in insulin requirement from baseline. The investigators reported a 62% decrease in insulin requirement in the treated group concomitant with a significant increase in C-peptide levels. The authors concluded from their BMSC transplantation results that they observed a "significant decrease in the insulin dose requirement along with improvement in the stimulated C-peptide levels in T2DM. However, more number of patients with a longer duration of follow-up are required to substantiate these observations."
In March 5th online edition of Cell Transplantation, E. W. Choi et al. from the Samsung Biomedical Research Institute (Seoul, Korea) published their studying the therapeutics in transplanting either syngeneic or allogeneic adipose-derived mesenchymal stem cells (AD-MSCs) into mice with experimental autoimmune thryoiditis. The investigators found that administering either syngeneic or allogeneic AD-MSCs were able to reduce thyroglobulin autoantibodies and suppress lymphocyte infiltration into the thryoid. Additionally, administration of either phenotype restored the Th1/Th2 balance in the recipient without any observable adverse events. However, allogeneic AD-MSCs induced a stronger humoral response compared to infused synegeneic AD-MSCs. The researchers surmise that this phenomenon may be attributed to stem cells using migrating to the spleen with their primary function in systemic immune modulation.
In the March 25th issue of Stem Cell Research & Therapy, M. Song et al. from the University of Pittsburgh School of Medicine published their experimental results on age-related decline in the regeneration potential of adult stem cells in skeletal muscle. The investigators used a mouse model of the genetic disease for premature aging, Hutchinson Gilford Progeria Syndrome (Zmpste24 mice). Muscle-derived stem/progenitor cells (MDSPCs) from the progeroid mice were shown to have reduced proliferation and myogenic differentiation. MDSPCs from Zmpste24 mice had impaired muscle regeneration capacity concomitant with limited engraftment potential when transplanted into dystrophic muscle compared to wild-type (MT) MDSPCs. Conversely, the researchers conducted experiments to demonstrate in vitro in which WT MDSPCs were able to rescue the myogenic defect in the progeroid MDSPCs. The data suggest that exogenous factors secreted by the WT stem cells can rescue the dysfunctional progeroid stem cells. The authors concluded from their study results that "adult stem/progenitor cell dysfunction contributes to impairment of tissue regeneration and suggest that factors secreted by functional cells are indeed important for the therapeutic effect of adult stem cells."
In the March issue of Cell Transplantation (22: 437-445), S.-H. Bhang et al. form Seoul National University (Korea) reported their study results on the administration of human adipose-derived stroma cells (hASCs) for dermal regeneration in skin wounds. The investigators conducted experiments to determine if co-administration of hASCs and platele-rich plasma (PRP) in avascular wounds. Athymic mice were used for determining the efficacy of skin regeneration with hASCs and in combination with PRP. The experimental results revealed that hASCs and co-administration of PRP significantly improved skin regeneration and hASCs proliferation at the wound site than either hASCs or PRP administered alone at the wound site. The authors noted that since PRP contain growth factors such as PDGF and VEGf, improved proliferation and survival of the hASCs may be attributed to secretion of angiogenic paracrine factors from locally administered hASCs and mouse host cells in the wound area.