In the November, 2014 issue of Biomaterials, M. I. Bury et al. from the Feinberg School of Medicine at Northwestern University reported their study results on using self-assembly peptide nanofibers on a pro-inflammatory urinary augmentation model to temper the innate immune response. The investigators used decellularized small intestine submucosa as a scaffold which they subsequently treated with anti-inflammatory peptide amphiphiles (AIF-PAs). With the scaffolds treated with AIF-PAs there were observed increase in angiogenic responses, limited tissue collagen accumulation, and modulation of macrophage and neutrophil responses in the regenerated bladder tissue. Treatment group exhibited lower levels of pro-inflammatory cytokine production and increase anti-inflammatory cytokine levels concomitant with a reduction in M1 macrophages levels and stabilized levels of M2 macrophages. The regenerated bladder had fewer incidences of tissue granuloma and bladder stone formation. The authors concluded that their study results "demonstrate that AIF-PAs can alleviate galvanic innate immune responses and provide a highly conducive regenerative milieu that may be applicable in a variety of clinical settings."
In the August 14th online advance publication of Stem Cells and Development, D.-S. Park et al. from the Research Institute for Peridontal Regeneration (Seoul, Korea) reported their study results on the effects of the fibroblast growth factor-2 (FGF-2) on collagen tissue regeneration by human bone marrow-derived stem cells (hBMSCs). The investigators found that hBMSCs cultures in the presence of FGF-2 (5 ng/ml) have enhanced colony-forming efficiency, proliferation, and more efficient in vitro differentiation into tissue lineages. Expansion of hBMSCs with FGF-2 resulted in enhanced levels of insoluble/soluble and hydroxyproline. FGF-2 was shown to downregulate mRNA expression for type I collagen and upregulate expression of type II and III collagen concomitant with activation of the lysl oxidase family of genes." Transplantation of FGF-2 treated hBMSCs into immunocompromised mice revealed significantly more collagen with well-organized structures 8 weeks post-transplantation. The authors concluded that "FGF-2 facilitated the collagen-producting potency of hBMSCs both in vitro and in vivo, rendering them more suitable for use in collagen regeneration in the clinical field."
In the August 5th publication of Stem Cell Research & Therapy, A. Lluciŕ-Valldeperas et al. from the Health Science Research Institute Germans Triasi Pujol (Barcelona, Spain) reported their study results on the effects of electrical stimulation of cardiomyocyte progenitor cells (CMPCs). The investigators used CMPCs isolated from the adult human atrial appendages which were exposed to a pulsed electrical field for 7 and 14 days (2-ms ef 25mV/cm at 1 Hz alternating current). The experimental results revealed that electrical stimulation modulated CMPC genes and protein expression. The data revealed GATA binding protein 4 (GATA4a) and myocyte enhancer factor 2A (MEF2A) are upregulated. Additionally, cardioregeneration potential of CMPCs improves with electrical stimulation. The authors concluded from their study results that "electrostimulated CMPCs may be best-equipped cells for myocardial integration after implantation."
In the August 11th online early publication of Stem Cells, S. Forostyak et al. from the Academy of Science of the Czech Republic reported their study results on transplanting human bone marrow mesenchymal stromal cells (MSCs) in a rodent model of amyotrophic lateral sclerosis (ALS). The investigators used superoxide dismutase 1 (SOD1) rats for studying changes in the ventral horn perineuronal nets (PNN) following intrathecal administration of the MSCs. In SOD1 rats, it was found that they had abnormal disorganized PNN structure around the spinal motorneurons having a different gene expression profile for Versican, Hapln1, Neurocan, and Tenascin-R. Transplantation of MSCs preserved PNN structure concomitant with enhanced survival of motorneurons. Additionally, the experimental results revealed higher levels of IL-1a and MCP-1 in the cerebral spinal fluid (CSF) of SOD1 rats. The researchers believed changes in cytokine levels in the CSF could serve as biological markers for prognosis, diagnosis, and assessing treatment efficacy for ALS. The authors concluded from their experimental observations that "The administration of human MSCs is a safe procedure that delays the loss of motor function and increases the overall survival of symptomatic ALS animals, by remodeling the recipients' pattern of gene expression and having neuroprotective and immunomodulatory effects."
In the July 30th online early publication of Cell Transplantation, M. Murakami et al. from the National Center for Geriatrics and Gerontology Research Institute (Obu, Japan) reported their study results on comparing mesenchymal stem cells (MSCs) from different tissue sources in their ability to regenerate dental pulp. The investigators used granulocyte-colony stimulating factor (G-CSF) for mobilizing dental pulp stem cells (MDPSCs), bone marrow stem cells (MBMSCs) and adipose-derived stem cells (MADSCs) from a dog. The experimental results demonstrated that the trophic effects of MDPSCs on angiogenesis, neurite extension, and migration were higher than with MBMSCs or MADSCs. Transplantation of MDPSCs produced higher volume of regenerated pulp concomitant with a higher density of vascularization and innervation than with MBMSCs and MDPSCs. However, the researchers found that collagenous matrix in the pulp had a greater amount of dentin sialophosphoprotein (DSPP) positive odontoblast-like cells when transplanted with MBMSCs (highest) and significantly higher with MADSCs compared to MDPSCs. The authors concluded from their study observations that "an alternative cell source for dental pulp/dentin regeneration are stem cells form bone marrow and adipose tissue."
In the August issue of Stem Cells Translational Medicine, M. Durand et al. from IRBA (Brétigny-sur-Orge Cedex, France) reported their study results on mice with bone injuries recovered at an accelerated rate when exposed to hypobaric hypoxia. The investigators housed adult male C57/Bl6J mice either in a hypobaric room (FiO2 at 10%) for 4 days or under normoxic conditions. A hind-limb unloading group was included in the study which a hole was drilled in the right femur in order to suspend the mice. The experimental results demonstrated that "delayed hypoxia enhanced bone-healing efficiency by increasing the closing of the cortical defect in the newly synthesized bone volume in the cavity by 55% and 35%, respectively." Additionally, the researchers using proteome and histomorphometric analyses found that the bone-healing was by natural processes and not from mobilization of MSC-derived progenitors. The authors also noted that "hind-limb unloading had minimal effect "beyond delayed hypoxia-enhanced bone-healing efficiency."
In the July 23rd issue of the Journal of Neuroscience, G. Lewandowski & O. Steward from the University of California, Irvine reported their study results on regenerating corticospinal axons after spinal cord injury (SCI). The investigators used a gene therapy approach by injecting intracortically into rats adeno-associated virus as a vector carrying the gene encoding for shRNA (AAVsh) which inhibits the expression of phosphatase and tensin homolog (PTEN/AAVshPTEN). Rats receiving AAVshPTEN alone were found not to exhibit improved motor function following cervical dorsal hemisection injuries (SCI) 10 weeks after the injury. However, the group receiving AAVshPTEN concomitant with injection of salmon fibrin at the injury site were shown to have improved motor function with significantly higher forelimb-reaching scores. Additionally, the group receiving AAVshPTEn and salmon fibrin had axons extending further caudally in the corticospinal tract (CST) than the controls or group receiving only AAVshPTEN. The authors concluded from their study observations that their "data suggest that the combination of PTEN deletion and salmon fibrin injection into the lesion can significantly improve voluntary motor function after SCI by enabling regenerative growth of CST axons."
In the June 5th online early publication of Medicine & Science in Sports & Exercise, K. Zou et al. from the University of Illinois reported their study results on mesenchymal stems rejuvenating skeletal muscle after resistance exercise in mice. The investigators had found that transgenic (Tg) mice overexpressing the transmembrane protein α7B integrin enhanced satellite cell and growth response to eccentric exercise. Muscle mesenchymal stem cells (mMSCs/Sca1+CD45-) isolated from α7Tg mice were dye-labeled and injected into skeletal muscle of wild type recipient mice. Post-injection the mice were either sedentary or subjected to eccentric exercise training (downhill running) on a treadmill 3X/week. The experimental results demonstrated that mMSCs did not directly fuse with existing muscle fiber but enhanced Pax7+ cell numbers and myonuclear content in existing muscle fibers in the group undergoing eccentric exercise training. Also, rip strength improved in the exercise group. However, mMSC transplantation did not enhance tissue repair and growth in the absence of exercise. The authors concluded from their study that "mMSCs contribute to beneficial changes in satellite cell expansion and growth in α7Tg muscle following eccentric exercise. Thus, MSCs that naturally accumulate in muscle following eccentric contractions may enhance the adaptive response to exercise."
In the April 22nd online advance publication of Cell Transplantation, S. Dhingra et al. from the University of Toronto published their study results on transduction of allogeneic smooth muscle cells (SMCs) with Interleukin -10 (IL-10) gene to enhance engraftment in a rat model with experimental-induced myocardial infarction. The investigators used three groups of rats injected into the infarct site with either unmodified autologous, unmodified allogeneic, or allogeneic smooth muscle cells transduced with IL-10 gene. In vitro and in vivo results demonstrated that SMCs expressing IL-10 increased the number of regulatory T cells (CD4+CD25+) and reduced the number of cytotoxic T cells (CD8+) concomitant with a reduction in the anti-allogeneic antibody response. Transplantation of both unmodified autologous SMCs and modified allogeneic SMCs were shown to improve ventricular function (fractional shortening) and left ventricular dimensions (wall thickness) compared to the control or unmodified allogeneic SMCs. The researchers also reported enhanced survival in the groups receiving unmodified autologous SMCs and modified allogeneic SMCs. The authors concluded from their study observations "that IL-10 gene therapy with allogeneic SMCs prevents detrimental allo-immune response in the recipient, thereby increasing the survival of transplanted allogeneic SMCs and more effectively restoring cardiac function."
In the July 10th online advance publication of Cell Stem Cell, K. N. Cosgun et al. from TU Dresden Faculty of Medicine (Dresden, Germany) reported their study results in developing a mouse strain as an animal model for analyzing engraftment of transplanted human hematopoietic stem cells (HSCs). The investigators developed immune-deficient mouse strains containing Kit mutations. Human HSCs were found to engraft efficiently in the Kit mutant mice without irradiation conditioning. The researchers reported that mutation of the Kit receptor "enables robust, uniform, sustained, and serially transplantable engraftment of human HSC in adult mice. Additionally, human HSCs demonstrated robust multilineage engraftment and self renewal in the mutant mice. Differential Kit expression resulted in identifying two functionally distinct subpopulations of human HSCs. The authors concluded that Kit mutations "open up stem cell niches across species barriers" which may have a significant potential and broad application in human HSC research.