Japanese scientists from the Nara Institute of Science and Technology (Ikoma, Japan), M. Abematsu et al., reported in the August 16th issue of J. of Clinical Investigation, their success in restoring hind limb function with transplanted neural stem cells (NSCs) in a mouse spinal cord injury (SCI) model. The ability to regenerate neurons from the transplanted NSCs required co-administration of valproic acid (VPA) at the tissue injury site. The investigators noted that VPA is histone deacetylase inhibitor which promote differentiation of transplanted NSCs into neurons. The researchers further noted that without VPA the lesion site with inflammatory cytokines would induce differentiation of NSCs into astrocytes. Since the NSCs were derived from the embryonic forebrains of transgenic mice, the researchers were able to track the transplanted NSCs which expressed green fluorescent protein (GFP) and luciferase at the lesion site. The experimental results revealed that the transplanted NSCs "reconstructed broken neuronal circuits as well as received and sent synaptic connections to endogenous neurons." Additionally, ablating the transplanted cells prevented recovery of hind limb motor function which supported the observation that NSC transplantation supplemented with VPA restored motor function. The authors concluded that "epigenetic status in transplanted NSCs can be manipulated to provide effective treatment for SCI."

In the July 27th online edition of Stem Cells, Spanish scientists S. Erceg et al. from CIPF (Valencia) reported their study results on using human embryonic stem cells (hESCs) that had been differentiated into oligodendrocyte and motorneuron progenitors (OPC and MP, respectively) on regenerating axonal neurons in a rat spinal cord injury model. Following spinal cord transection, the investigators immediately transplanted OPCs and MPs into the injury site. The researchers observed that both the OPCs and MPs survived engraftment as well as migrated and differentiated into mature oligodendrocytes and neurons. In vivo functional electrophysiological assays concomitant with the Basso-Beattie-Bresnahan scores confirmed the ability of the differentiated progenitors to regenerate neurons and restore locomotor function when compared to controls. The authors concluded that "OPC and MP derived from hESC could be a useful therapeutic strategy to repair injured spinal cord."

In the August 2nd online edition of PNAS, A. M. S. Müller et al. from Stanford University School of Medicine published their results on a study in which they compared hematopoietic reconstitution following transplantation of either pure hematopoietic stem cells (HSCs) or grafts of HSCs supplemented with T cells having a mismatch of a minor histocompatability antigen in mice. The goal of the study was to determine the effects of each blood cell type and their role in immune regeneration during engraftment. The researchers conducted cell counts, blood composition, and chimerism of blood and lymphoid organs post-engraftment for up to one year. The experimental results revealed that recipients receiving grafts of pure HSCs showed superior total cell recovery and lymphoid reconstitution than recipients receiving grafts containing T cells. The study results suggested that the allogeneic T cells suppressed hematopoiesis in the HSCs and immune recovery. The authors concluded that their "observations contradict the postulation that mature donor T cells provide important transient immunity and facilitate HSC engraftment."

In the June 25th online edtion of the American J. of Pathology, S. A. Rogers et al. from Washington University School of Medicine reported the results of their study on xenotransplantation of procine islets and pig pancreatic primordia (embryonic day 28) into streptozotocin-treated diabetic rats. The investigators conducted experiments demonstrating normalization of glucose tolerance and without immune suppression. Porcine islets were engrafted into the renal capsule concomitant with pancreatic primordia transplanted into the mesentery. In situ hybridization analysis for porcine X chromosome revealed long-term donor cell engraftement. However, islet engraftment did not occur without transplantation of the E28 pig pancreatic primordia in the mesentery. The authors concluded from their study results that "tolerance induction to a cell component of porcine islets is induced by previous transplantation of E28 pig pancreatic primordia" in an immunocompetent animal.

In the June 4th issue of Cell Stem Cell, M. Zawadzka et al. from the University of Cambridge (UK) conducted a study discerning the origins of remyelinating cells following central nervous system (CNS) demyelination (in diseases such as multiple sclerosis). The published experimental results showed that PDGFRA+/NG2 neural stem/progenitor cells in adult CNS appear to generate remyelinating oligodendrocytes following demeylination. With Cre-lox fate mapping in transgenic mice, the experimental data showed that most Schwann cells remyelinating the CNS axons are derived from the CNS precursors. Although some of the neural progenitors are able to generate some new astrocytes following a chemically induced lesion in the brain, the investigators found that the majority of the reactive astrocytes encompassing the lesions are derived from pre-existing FGFR3-expressing cells (astrocytes). The authors concluded from their observations that cells contributing the CNS remyelination are CNS progenitors and surprisingly their ability "to generate Schwann cells, which normally develop from the embryonic neural crest and are restricted to the peripheral nervous system."

Japanese scientists from the Institute for Advanced Medical Sciences (Hyogo, Japan), A. Nakano-Doi et al., published in June 1st online edition of Stem Cells the results of their study on the contribution of bone marrow mononuclear cells (BMMCs) during regeneration of ischemic brain tissue following experimentally induced stroke in mice. The investigators conducted intravenous transplantation experiments focusing on the contribution of BMMCs to responses of endothelial cells (ECs) and neural stem/progenitor cells (NSPCs) following systemic administration of a million BMMCs 2 days after cortical infarction. The experimental data revealed that BMMCs administration enhanced proliferation and angiogenesis of ECs as well as proliferation of NSPCs compared to untreated animals. In endostatin-treated (an inhibitor of EC proliferation) animals, NSPC proliferation was suppressed which suggests that NSPC proliferation is regulated by the vascular niche following a cerebral infarction through the contribution of systemically administered BMMC on EC proliferation.

In the June issue of Experimental Hematology, A. D. Goodrich et al. reported their study results transplanting human embryonic stem cell-derived CD34+ into fetal sheeps. The rationale of the study was based on the supposition that intraperitoneal/in utero injections prior to development of the immune system would induce tolerance to the xenografts. The experimental results revealed that human cells were found in the sheep up to 5 years post transplantation. Additionally, human DNA and mRNA for human insulin were detected in the sheep pancreas. An average of 1.51 ng/ml of C-peptide were detected in the serum in 8 animals receiving differentiated CD34+ cells up to 55 months post-transplantation. The researchers reported that as few as 23,500 cells resulted in "long-term sustainable β-cell-like activity."

In the May 14th issue of Cell, K. Oshima et al. from Stanford University School of Medicine published their study results for differentiating pluripotent stem cells into otic hair cells. The investigators were able to used both mouse embryonic and induced pluripotent stem cells to differentiate in vitro, using a step-wise induction protocol, the cells into otic progenitors. In order to differentiate the cells into an ectodermal germ layer lineage phenotype, the investigators inhibited Wnt/TGFβ signaling in the pluripotent stem cells. Subsequently, the ectodermal linege committed cells were committed to differentiate into otic progenitors by activating the FGF signaling pathway. The researchers guided the otic progenitors to differentiate them into epithelial clusters with hair cell-like morphology having stereociliary bundles. These bundle-bearing cells responded to mechanical stimulation and reflected the immature hair cell phenotype in its ability to transduce currents.

In the May 14th online edition of the J. Cellular and Molecular Medicine, R. Carmona et al. from the University of Málaga (Spain) published their study results isolating and characterizing a population of free-floating cells in the coelemic cavity during peritoneal regeneration. The invesitgators noted that the peritoneal mesothelium has remarkable regenerative capacity following injury. With murine model, the experimental results demonstrated that GFP-labelled bone marrow cells appears to infiltrate the injury site 24 hrs. after peritoneal injury. Immunohistochemical staining revealed that the injured peritoneal wall consisted onf GFP+ cells also expressing the mesothelial (mesothelin, cytokeratin) and fibroblastic (FSP1) markers as well as expressing procollagen-1 and smooth muscle &alpah;-actin. The researchers designated these cells as peritoneal repairing cells (PRCs), which are abundant in both the damaged and uninjured area of the peritoneal wall one week after surgery. However, the investigators found that the PRCs become very scarce after the mesothelium has completely healed one month after injury. The authors concluded from their study results "that the PRC constitute a type of monocyte-derived cells, closely related with tissue-repairing cells know as fibrocytes" during "peritoneal reparation."

Scientists from Yale University School of Medicine, E. F. Wolff et al., published in the April 7th online edition of the J. Cellular and Molecular Medicine the results of their study on the ability to differentiate endometrial stem cells into dopaminergic neurons. Adult human endometrial-derived stem cells (HEDSCs) were reported to have a mesenchymal stem-like phenotype expressing CD90, PDGF-Rβ and CD146. Differentiated HEDSCs also expressed the neural markers nestin and tyrosine hydroxylase. Patch clamp experiments showeed that the differentiated HEDSCs have GIRK2 channels; a characteristic of neurons found in the brain. In an MPTP (methyl-4-phenyl-1,2,5,6-tetrahydropyridine) induced immunocompriomised mouse model of Parkinson's disease (PD), labeled HEDSCs transplanted into the MPTP-treated mice migrated to the site of the lesion and significantly increased the levels of striatal dopamine. The authors concluded from their observations that HEDSCs "are a highly inducible source of allogeneic stem cells that rescue dopamine concentrations in an immunocompetent PD mouse model."