In the December issue of Stem Cell Research & Therapy, W.-J. Zhange et al. from China-Japan Friendship Hospital (Beijing, China) published their study results on expanding and differentiating human fetal pancreatic progenitor cells into insulin-producing cells. The investigators expanded the fetal progenitor cells in a culture medium containing fibroblast growth factor (bFGF) and leukemia inhibitor factor (LIF). Following ex vivo expansion, the pancreatic progenitor cells were differentiated into insulin-producing cells with nicotinamide, all-trans retinoic acid, glucagon-like peptide-1, and activin A (introduced during the last week of cultivation). The researchers found ha the differentiated cells expressed insulin, glucagon, glucose transporter 1(GLUT1), GLUT2, and voltage-dependent calcium channel (VDCC). Additionally, the experimental results demonstrated that the aggregated islet-like structures expressed higher level of insulin than adherent monolayer cultures. The aggregated cells transplanted into diabetic nude mice maintained normoglycemia. The authors concluded from their study results that "human fetal pancreatic progenitor cells have a good capacity for generating producing cells and provide a promising potential source for diabetes treatment."
In the November 17th early online publication of Nature Biotechnology, L. Baeyens et al. from the University of California, San Francisco published their experimental results on using cytokines to reprogram pancreatic exocrine (acinar) cells into beta-like cells. The investigators administered epidermal growth factor and ciliary neutrophic factor into adult mice with chronic hyperglycemia. Epigenetically reprogramming of terminally differentiated acinar resulted in the generation of functional beta-like cells which were glucose responsive. The treated diabetic mice were able to maintain normoglycemia for up to 248 days. The researchers found that reprogramming of acinar cells were dependent upon Stat3 signaling and a threshold number of Neurogenin 3 (Ngn3)-expressing acinar cells. The authors concluded from their experimental observation that their approach of transient exposure of cytokines in vivo was a more efficient method for reprogramming acinar-to-beta cell than using viral vectors for delivering exogenous transcription factors.
In the December issue of Stem Cells Translational Medicine, S. S. Bedi et al. from the University of Texas, Houston reported their study results on the mechanism by which intravenous infusion of bone marrow-drived multipotent adult progenitor cells (MAPCs) attenuates inflammation following traumatic brain injury (TBI) in rodents. The investigators infused MAPCs (2 and 10 million cells per kilogram) 2 and 24 hours after cortical contusion injury (CCI). The experimental data revealed that the rats receiving 10 million MAPCs (CCI-10) had significant improvement in motor function and improved memory. The researchers also observed signification decrease in the number of activated microglia cells in the dentate gyrus inf the CCI-10 group compared to controls. The authors concluded that their "results demonstrate that intravenous MAPC treatment after TBI in a rodent model offers long-term improvement in spatial learning as well as attenuation of neuroinfammation."
In the August 30th online early publication of Cell Transplantation, H. Iwai et al. from Keio University School of Medicine (Tokyo, Japan) published their study results on determining the optimal transplantation site of neural stem/progenitor cells (NS/PCs) in the spinal cord injury (SCI). The investigators used wild-type mice with contusive SCI at the T10 level and NS/PCs-labelled cells from fetal transgenic mice. NS/PCs were tranplanted at either the lesion epicenter (E), or at rostral and caudlal (RC) sites. Motor functional recovery was improved at either of the above transplantation sites compared to saline controls. However, quantitative RT-PCR analyses revealed that brain-derived neurotrophic factor expression was higher in the RC transplantation site than in the E segment. However, the researchers noted that the "location of the transplanjtation site did not affect the area of spared fibers, angiogenesis, or the expression of any other mediators" The authors concluded from their study observation that "the micro-environments of the E and RC sites are able to support NC/PCs transplanted during the sub-acute phase of SCI" equally. They also noted that "optimally, a certain threshold number of NC/KPCs should be grafted into the E segment to avoid damaging sites adjacent to the lesion during the injection procedure."
In the October 21st online early publication of Cell Transplantation, M. Dubsky et al. from the Institute for Clinical and Experimental Medicine (Prague, Czech Republic) reported the results of their clinical study on the serum levels of pro-angiogenic cytokines and angiogenic inhibitors following stem cell therapy in 25 diabetic patients with critical limb ischemia. The investigators injected autologous bone marrow or stimulated peripheral blood stem cells and determine serum levels of pro-angiogenic cytokines (VEGF, b-FGF, Ang-1, PDGF-AA and PDGF-BB) and anti-angiogenic cytokine (Endostatin) and evaluated 6 months after treatment. After 1 and 3 months, the researchers observed an increase in angiogenic inhibitor Endostatin which correlated with the number of injected CD34+ cells. Conversely, there was no significant increase in the serum levels of pro-angiogenic cytokines after stem cell therapy. The authors concluded from their study results that following treatment with stem cells they observed a "significant increase in serum levels of angiogenic inhibitor Endostatin which correlated with the number of injected CD34+ cell;" which they suggested "can possibly reflect a feedback regulation of angiogenesis."
In the October 29th online early publication of Cell Proliferation, C. Zhou et al. from Sichuan, University (Chengdu, China) reported their study results on the effects of BMP4 on promoting vascularization of human adipose stromal cells (ASCs) and endolthelial cells both in vitro and in vivo. The investigators noted that adipose tissues contain an abundance of ASCs. The ASCs can give rise to pericyte which were identified by immunoflourescence staining for a-SMA and PDGFR-b. When the ASCs were seeded onto 3D cultures containing collagen-fibronectin gels and endolthelial cells. The authors showed that ASCs promoted vascularization and BMP4 enhanced the effect.
In the October 21st online early publication of Cell Transplantation, D. Xu et al. from Stanford University School of Medicine published their study results on the development of a novel method for differentiating adipocyte-derived stem cells (ASCs) into hepatocyte-like cells (iHeps). The investigators used a "hanging drop method" for generating spheroid aggregates ("spheres") from ASCs. After 2 days in culture, the spheres were seeded onto matrigel-coated dishes and chemically induced in a two-step process for differentiating the spheres into hepatocytes (iHeps). The iHeps were shown to exhibit properties of hepatocytes (expressing CK8/18, glycogen synthesis, ablumin secretion, and urea production). The iHeps were subsequently transplanted into damaged liver of transgenic mice and integrated into murine liver concomitant with the production human albumin in the serum. Additionally, the transplanted iHeps do not form tumors. The authors concluded from their study results that "functioning human liver tissue could be generated in vivo after direct implantation of ASC-derived cells into the liver."
In the October 17th online early publication of Cell Stem Cell, R. P. Fordham et al. from the University of Cambridge (UK) published their study results on analyzing the stem cells in human and mouse fetal intestines. The investigators reported that the small intestine has a transient population of highly proliferative progenitors which in vitro can form fetal enterospheres. Maturation of fetal intestinal progenitors requires exposure to Wnt and in vitro form mature intestinal organdies. Human induced pluripotent stem cells (hIPSCs) which were differentiated into intestinal progenitors formed enterospheres (FEnS) in vitro. The researchers also reported that mouse fetal intestinal progenitors expressed lower levels of Lgr5 than mature progenitors. In a colonic injury model. transplantation of fetal progenitors were shown to regenerate the intestinal epithelium. Transplantation of FEnS onto the injured colon contributed to the regeneration of colonic epithelium "by forming epithelial crypt-like structures expressing region-specific differentiation markers."
In the September 2nd publication of Stem Cell Research & Therapy, H. B. Henriksson et al. from the Gothenburg University (Sweden) reported their experimental results on the migration patterns of stem cells from the intervertebral disc (IVD) and knee joints (KJs) of rabbits and their ability to regenerate cartilage. The investigators used FACS-sorted, flourescein-labelled GDF5+) cells from the IVD explants to observe migration patterns and the distance traveled in vitro. The experimental results showed that GDF5+ cells displayed the best migration capability in IVD explants. BrdU+ cells were found in early time points in niches of the KJs and at later time points in articular cartilage (AC). The authors noted that their study results "indicate similar cellular migration patterns in cartilage regions (IVD and KJs) with migration from stem cell niche areas into mature cartilaginous tissues of both the KJs and the IVD.
October 28: Autologous Fat Graft in Systemic Sclerosis
In the October 22nd online early publication of Cell Transplantation, N. Del Papa et al. from the Day Hospital Reumatologia, Ospedale (Milan, Italy) reported their results on a 20-patient, clinical study using autologous fat tissue grafting (AFTG) in patients with advanced systemic sclerosis (SSc)-related perioral thickening and mouth opening. The aim of the study was to determine if AFTG of the lips improved mouth opening in patients with SSc. Measurements of microvasculature architecture and density (immunohistochemical stains with anti-CD34/CD31). The investigators found that 3 months after treatment, the "inter-incisal distance and oral perimeter significantly increased (p<0.001)." Additionally, the researchers noted that vidocapaillaroscopy images showed significant increased in skin neovascularization (p<0.001) which was confirmed by perioral skip biopsy sections. The authors concluded that their "present study suggests that, in patients with SSc, ATFG can improve mouth opening and function, induce neovasculariztion, and partially restore the skin structure."