Androgen receptors are expressed in a variety of human fetal extragenital tissues： an immunohistochemical study

Aim： To investigate the expression of androgen receptors in the extragenital tissues of developing human embryo. Methods： Using immunohistochemistry, we investigated the distribution of androgen receptor （AR） in the extragenital tissues of paraffin-embedded tissue sections of first trimester （8-12 weeks gestation） human embryos. Gender was determined by polymerized chain reaction. Results： There were no differences in the expression and distribution of AR in male and female embryos at any stage of gestation. AR expression was seen in the thymus gland. The bronchial epithelium of the lungs showed intense positive staining with surrounding stroma negative. Furthermore, positive staining for androgen receptor was exhibited in the spinal cord with a few positive cells in the surrounding tissues. Cardiac valves also showed strong positive staining but with faint reactivity of the surrounding cardiac muscle. There was no staining in kidney, adrenal, liver or bowel. Conclusion： This study demonstrates that immunoreactive AR protein is present in a wide variety of human first trimester fetal tissues and shows the potential for androgen affecting tissues, which are mostly not considered to be androgen dependent. Moreover, it implies that androgen might act as atrophic factor and affect the early development of these organs rather than simply sexual differentiation.

Differentiation and functional connectivity of fetal tectal transplants

Data from studies analyzing the differentiation and functional connectivity of embryo nic neural tissue grafted into the mammalian nervous system has led to the clinical testing of the fetal graft approach in patients with neurodegenerative disease.While some success has been achieved,ethical concerns have led to a search for alternative therapeutic strategies,mostly exploring the use of neural precursors or neurons derived from pluripotent stem cells to replace damaged host neurons and restore lost circuitries.These more recent studies address questions of graft viability,differentiation,and connectivity similar to those posed by researchers in earlier fetal transplant work,thus reviews of the fetal graft literature may inform and help guide ongoing research in the stem cell/organoid field.This brief review describes some key observations from research into the transplantation of neural tissue into the rat visual syste m,focusing on grafts of the fetal supe rior colliculus(tectal grafts) into neonatal or adult hosts.In neonate hosts,grafts quickly develop connections with the underlying host mid b rain and attain a morphology typical of mature grafts by about 2 weeks.G rafts consistently contain numerous localized regions which,based on neurofibrillar staining,neuronal morphology(Golgi),neurochemistry,receptor expression,and glial architecture,are homologous to the stratum griseum supe rficiale of normal superior colliculus.These localized "patches" are also seen after explant culture and when donor tectal tissue is dissociated and reaggregated prior to transplantation.In almost all circumstances,host retinal innervation is restricted to these localized patches,but only those that are located adjacent to the graft surfa ce.Synapses are formed and there is evidence of functional drive.The only exception occurs when Schwann cells are added to dissociated tecta prior to reaggregation.In these co-grafts,the peripheral glia appear to compete with local target fa ctors and host retinal ingrowth is more widespread.Other afferent systems(e.g.,host co rtex,serotonin) show different patterns of innervation.The host cortical input originates more from extrastriate regions and establishes functional excitato ry synapses with grafted neurons.Finally,when grafted into optic tra ct lesions in adult rat hosts,spontaneously regrowing host retinal axons retain the capacity to selectively innervate the localized patches in embryonic tectal grafts,showing that the specific affinities between adult retinal axons and their targets are not lost during regeneration.While the research described here provides some pertinent information about development and plasticity in visual pathways,a more general aim is to highlight how the review of the extensive fetal graft lite rature may aid in an appreciation of the positive(and negative) fa ctors that influence survival,differentiation,connectivity and functionality of engineered cells and organoids transplanted into the central nervous system.

Combined cell-based therapy strategies for the treatment of Parkinson's disease:focus on mesenchymal stromal cells

Parkinson’s disease is a neurodegenerative condition characterized by motor impairments caused by the selective loss of dopaminergic neurons in the substantia nigra.Levodopa is an effective and well-tolerated dopamine replacement agent.However,levodopa provides only symptomatic improvements,without affecting the underlying pathology,and is associated with side effects after long-term use.Cell-based replacement is a promising strategy that offers the possibility to replace lost neurons in Parkinson’s disease treatment.Clinical studies of transplantation of human fetal ventral mesencephalic tissue have provided evidence that the grafted dopaminergic neurons can reinnervate the striatum,release dopamine,integrate into the host neural circuits,and improve motor functions.One of the limiting factors for cell therapy in Parkinson’s disease is the low survival rate of grafted dopaminergic cells.Different factors could cause cell death of dopaminergic neurons after grafting such as mechanical trauma,growth factor deprivation,hypoxia,and neuroinflammation.Neurotrophic factors play an essential role in the survival of grafted cells.However,direct,timely,and controllable delivery of neurotrophic factors into the brain faces important limitations.Different types of cells secrete neurotrophic factors constitutively and co-transplantation of these cells with dopaminergic neurons represents a feasible strategy to increase neuronal survival.In this review,we provide a general overview of the pioneering studies on cell transplantation developed in patients and animal models of Parkinson’s disease,with a focus on neurotrophic factor-secreting cells,with a particular interest in mesenchymal stromal cells;that co-implanted with dopaminergic neurons would serve as a strategy to increase cell survival and improve graft outcomes.