Neuroprotective effects of human umbilical cord mesenchymal stromal cells in an immunocompetent animal model of Parkinson's disease.

Microglial activation in the substantia nigra (SN) is a ubiquitous feature in PD which could mediate toxic effects. Human mesenchymal stromal cells (hMSCs) possess immunomodulatory properties. We evaluated whether the transplantation of hMSCs obtained from umbilical cord had a neuroprotective effect in a not-immunosuppressed rat Parkinson's disease (PD) model. Rats receiving hMSCs in the SN displayed significant preservation in the number of dopaminergic neurons in the SN at 21 days after lesion and an improved performance in behavioral tests compared to control rats. However, no differences in any inflammatory parameter tested were found. These results suggest that grafted hMSCs exert neuroprotection but not neuromodulatory effects on degenerating dopaminergic neurons.

Effect of whole bone marrow cell infusion in the progression of experimental chronic renal failure.

INTRODUCTION: The therapeutic potential of adult stem cells for the treatment of chronic diseases is becoming increasingly evident over the last few years. In the present study, we sought to assess whether the infusion of bone marrow-derived mononuclear cells (MoSCs) and mesenchymal cells (MSCs) could reduce/stabilize the rate of progression of chronic renal failure (CRF) in rats. METHODS: We used the 5/6 renal mass reduction model to induce chronic renal failure in male Wistar rats. Renal function was assessed by measurements of serum creatinine (sCr), creatinine clearance (Clcr), and 24-hour proteinuria at baseline as well as 60 and 120 days after surgery. MoSCs and MSCs obtained from bone marrow aspirates were separated by the Ficoll-Hypaque method. After a 12- to 14-day culture, 1.5 x 10(6) MSCs and the same number of MoSCs were injected into the renal parenchyma of the remanant kidney of rats with CRF on the day of surgery. RESULTS: Among the control group, at day 120, the results were sCr = 1.31 +/- 0.5 mg/dL, Clcr = 0.64 +/- 0.35 mL/min, and proteinuria = 140.0 +/- 57.7 mg/24 h. Rats treated with MoSCs at day 120 had sCr = 0.81 +/- 0.20 mg/dL, Clcr = 1.05 +/- 0.26 mL/min, and proteinuria = 61 +/- 46.5 mg/24 h, while rats injected with MSCs had sCr = 0.95 +/- 0.1 mg/dL, Clcr = 0.68 +/- 0.24 mL/min, and proteinuria = 119.2 +/- 50.0 mg/24 h. Analysis of the progression to CRF showed that the treatment significantly reduced the rate of decline in Clcr after treatment with MoSc: control: -0.0049 +/- 0.0024 mL/min/d versus MSC: - 0.0013 +/- 0.0017 mL/min/d versus MoSC: +0.0002 +/- 0.0016 mL/min/d (P = .017). Proteinuria tended to be lower among the treated groups. Histological scores of chronic damage were not different, but distinct patterns of chronic lesions were observed among treated rats. CONCLUSION: Our results showed that progression of CRF in rats could be slowed/stabilized by intrarenal parenchymal injection of MoSCs. A trend toward reduction in the progression rate of CRF was also observed with injection of MSCs.

Experimental studies on a lethal gene (1) in the Mexican axolotl, Ambystoma mexicanum.

1. Gene l is a recessive lethal factor found in the white strain of axolotls. Animals heterozygous for the gene are phenotypically normal. When mated with each other they give offspring 25% of which exhibit the lethal effects of the gene. 2. The l/l homozygotes develop normally to an advanced embryonic stage (Harrison stage 40) before the effects of the gene are first manifested. They then come to display a characteristic combination of abnormalities, including a disproportionately small head, small and poorly developed eyes, abnormal poorly developed gills, undifferentiated limb buds, and reduced overall growth rate. They may feed briefly, but soon stop and invariably die within a few weeks of the time of hatching. 3. The action of gene l has been analyzed by parabiosing mutant and normal embryos, and by grafting various organ primordia reciprocally between mutant and normal embryos. Parabiosis to normal embryos fails to correct the abnormalities of the mutants, although their survival may be somewhat prolonged. Grafts of mutant organ primordia (eye, limb, gill, pronephros, gonad, head) also invariably fail to show improved development or to survive on normal hosts; normal organ primordia develop normally on mutant hosts so long as the mutant survives. These experiments indicate that gene l is a recessive autonomous cell lethal affecting all of the organ systems during late embryonic and early larval development.