Transplanted neuronal precursors migrate and differentiate in the devel-oping mouse brain

The subventricular zone (SVZ), lining the lateral ventricle in forebrain, retains a population of neuronal precursors with the ability of proliferation in adult mammals. To test the potential of neuronal precursors in adult mice, we transplanted adult SVZ cells labeled with fluorescent dye PKH26 into the lateral ventricle of the mouse brain in different development stages. The preliminary results indicated that the grafted cells were able to survive and migrate into multiple regions of the recipient brain, including SVZ, the third ventricle, thalamus, superior colliculus, inferior colliculus, cerebellum and olfactory bulb etc; and the amount of survival cells in different brain regions was correlated with the development stage of the recipient brain. Immunohistochemical studies showed that most of the grafted cells migrating into the specific target could express neuronal or astrocytic marker. Our results revealed that the neuronal precursors in adult SVZ still retained immortality and ability of prolife     

建立同种异体猪胰腺移植动物模型的手术实验体会

着重对猪的同种异体胰腺移植手术过程,以及如何保证移植成功的若干环节,进行了较为详尽的阐述。     

Reversal of new-onset type 1 diabetes in mice by syngeneic bone marrow transplantation

Autologous hematopoietic stem cell transplantation (HSCT) has recently been performed as a novel strategy to treat patients with new-onset type 1 diabetes (T1D). However, the mechanism of autologous HSCT-induced remission of diabetes remains unknown. In order to help clarify the mechanism of remission-induction following autologous HSCT in patients with T1D, mice treated with multiple low doses of streptozotocin to induce diabetes were used as both donors (n = 20) and recipients (n = 20). Compared to streptozocin-treated mice not receiving transplantation, syngeneic bone marrow transplantation (syn-BMT) from a streptozocin-treated diabetic donor, if applied during new-onset T1D (day 10 after diabetes onset), can reverse hyperglycemia without relapse (P < 0.001), maintain normal blood insulin levels (P < 0.001), and preserve islet cell mass. Compared to diabetic mice not undergoing HSCT, syn-BMT, results in restoration of Tregs in spleens (P < 0.01), increased Foxp3 mRNA expression (P < 0.01) and increased Foxp3 protein expression (P < 0.05). This diabetic-remission-inducing effect occurred in mice receiving bone marrow from either streptozocin-treated diabetic or non-diabetic normal donors. We conclude that autologous HSCT remission of diabetes is more than transient immune suppression, and is capable of prolonged remission-induction via regeneration of CD4+CD25+FoxP3+ Tregs.     

Assessing the short-term response of stream diatoms to acidity using inter-basin transplantations and chemical diffusing substrates

1. Acid‐base status has major effects on diatoms, but there is little information on their short‐term response to changing acidity. This is despite the use of diatoms as bioindicators in streams where acid episodes are important during rainstorms (hours to days) or snowmelt (days to weeks). In the Llyn Brianne experimental catchments (Wales, UK), we attempted to mimic the effects of short‐term acidification by (i) reciprocally transplanting diatoms between two streams of contrasting acidity and (ii) using acid‐diffusing substrates. 2. Diatom diversity decreased rapidly on substrata transplanted from the circumneutral into the acidic stream, and increased in the reciprocal transplantation. Changes in dominant taxa occurred within three days in the acidic stream because of the rapid growth of Eunotia exigua, and by nine days in the circumneutral stream because of the proliferation of Achnanthidium minutissimum. Transplants were near indistinguishable from ambient assemblages by day 12. 3. There were no effects of enclosures on assemblage composition, but diatoms responded more rapidly to altered chemistry in enclosures with coarse mesh (26 × 50 mm) than finer mesh (320 μm). 4. Chemical diffusing substrates comprised terracotta tiles attached to dosing reservoirs that created locally acid (using H₂SO₄) or metal‐rich conditions (using MnSO₄) in the circumneutral stream over 26 days. Diatom responses were compared with reference substrates dosed with deionised or circumneutral stream water, and we also assessed whether effects were moderated by macroinvertebrate grazers. 5. Surface pH was lower by 1–2 pH units on acid‐dosed substrates than on reference tiles or in surrounding streamwater. Grazed assemblages on acid‐dosed substrates differed significantly from ungrazed reference assemblages, acquiring significantly greater relative abundance of Eunotia spp. However, the magnitude of response was less than in the between‐stream transplantations either because (i) metal exposure and base cation concentrations differed between the transplants and dosing substrates or (ii) diatom response to reduced pH on the diffusing substrates was restricted by the scarcity of acidobiontic diatoms in the circumneutral stream. Similar filter, founder or dominance effects might also affect diatom responses to real acid episodes. 6. These data show that diatom assemblages can respond rapidly and directly to changes in acid‐base status, but short‐term acidification might affect diatoms more rapidly than subsequent recovery. Because the experimental methods used were imperfect representations of episodic effects, diatom response to real acid events requires further field evaluation.     

CD95 signaling deficient mice with a wild-type hematopoietic system are prone to hepatic neoplasia

Patients with mutations in the death receptor CD95 (Fas/APO-1) frequently develop B-cell lymphoma. However, solid tumors have not been found in the context of defective CD95. This could be due to the fatal autoimmune proliferative disease that develops in the absence of functional CD95 or to a difference in CD95 signaling in lymphoid versus nonlymphoid tissues. To test this we reconstituted mice that harbor a point mutation in the death domain of CD95 (lpr^cg mice), either in one or in both alleles, with bone marrow from wild-type (wt) mice. After a year one third of the lpr^cg/lpr^cg mice developed spontaneous hepatic neoplasms. In contrast only one of the wt/lpr^cg mice and none of the wt mice developed liver cancer. The agonistic anti-CD95 antibody Jo2 induced massive apoptosis in the liver of wt mice but not in the livers of either wt/lpr^cg or lpr^cg/lpr^cg mice. The susceptibility of lpr^cg/lpr^cg mice to liver cancer cannot solely be due to impaired CD95 mediated apoptosis because there was no clear correlation between apoptosis resistance and tumor formation. A gene chip analysis identified genes selectively upregulated in the liver of wt and wt/lpr^cg mice which may protect these mice from developing liver cancer. Our data represent the first case of CD95 protecting from developing a solid cancer. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Transplantation of adult neural progenitor cells transfected with vascular endothelial growth factor rescues grafted cells in the rat brain

Growth factors are currently evaluated as therapeutics in stroke and neurodegeneration. Besides direct neurotrophic effects, they promote proliferation, survival, and differentiation of both transplanted and endogenous neural precursor cells (NPCs). In the current study, we investigated whether NPCs expressing Vascular Endothelial Growth Factor VEGF-A165 are a useful vehicle for growth factor delivery after transplantation into the caudate putamen of the rat brain. We found an increased survival of adenovirally transfected NPCs after 11 days, but not after 24 hours or 4 days. Additional brain immunohistochemistry revealed increased expression of the endothelial cell marker PECAM-1 (CD31) after 24 hours, 4 day, and 11 days after transplantation. In conclusion, we show that the graft itself is a useful vehicle for growth factor delivery, promoting the survival of NPCs. Moreover, transplantation of VEGF-expressing NPCs supports angiogenesis in the brain, which may contribute to potential brain repair.     

Cost of adaptation to a metalliferous environment for Thlaspi caerulescens: a field reciprocal transplantation approach

Field reciprocal transplantations of two metallicolous populations (Mpops) and two nonmetallicolous populations (NMpops) of Thlaspi caerulescens were performed here to determine the pattern of local adaptation and to assess the cost of adaptation of Mpops to a metalliferous environment (Menv). The role of herbivores as an important selective pressure in the nonmetalliferous environment (NMenv) was also examined. Growth, survival, fitness, life cycle and herbivore consumption were monitored for each transplant for 2 yr. Local adaptation of Mpops to their own environment was clearly demonstrated, as Mpops consistently outperformed NMpops in Menv. In NMenv, no advantage of NMpops over Mpops was detected. However, the fitness of Mpops was generally lower in NMenv than in Menv. Herbivore consumption appeared to be a significant selective pressure for Mpops in NMenv. An imbalance of selective forces between Menv and NMenv probably explains the greater local adaptation of Mpops. Therefore, colonization of NMenv by Mpops appears possible. Although Mpops were able to survive and reproduce in NMenv, they nevertheless expressed a cost attributable in part to their higher susceptibility to herbivores.     

Efficacy and safety of autologous stem cell transplantation for decompensated liver cirrhosis: A retrospective cohort study

AIM To evaluate the long-term efficacy and safety of autologous stem cell transplantation(SCT) for decompensated liver cirrhosis.METHODS Consecutive patients with decompensated liver cirrhosis were included and assigned into the SCT group and non-transplantation(non-SCT) group according to whether they received SCT treatment. Patients werefollowed up for ten years. The long-term survival rate and incidence of hepatocellular carcinoma(HCC) were compared between groups.     

Regeneration of functional alveoli by adult human SOX9+ airway basal cell transplantation

Irreversible destruction of bronchi and alveoli can lead to multiple incurable lung diseases. Identifying lung stem/progenitor cells with regenerative capacity and utilizing them to reconstruct functional tissue is one of the biggest hopes to reverse the damage and cure such diseases. Here we showed that a rare population of SOX9⁺ basal cells (BCs) located at airway epithelium rugae can regenerate adult human lung. Human SOX9⁺ BCs can be readily isolated by bronchoscopic brushing and indefinitely expanded in feeder-free condition. Expanded human SOX9⁺ BCs can give rise to alveolar and bronchiolar epithelium after being transplanted into injured mouse lung, with air-blood exchange system reconstructed and recipient’s lung function improved. Manipulation of lung microenvironment with Pirfenidone to suppress TGF-β signaling could further boost the transplantation efficiency. Moreover, we conducted the first autologous SOX9⁺ BCs transplantation clinical trial in two bronchiectasis patients. Lung tissue repair and pulmonary function enhancement was observed in patients 3–12 months after cell transplantation. Altogether our current work indicated that functional adult human lung structure can be reconstituted by orthotopic transplantation of tissue-specific stem/progenitor cells, which could be translated into a mature regenerative therapeutic strategy in near future.