{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T04:21:18Z","timestamp":1741753278636,"version":"3.38.0"},"reference-count":58,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2014,3,1]],"date-time":"2014-03-01T00:00:00Z","timestamp":1393632000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cell Transplant"],"published-print":{"date-parts":[[2014,3]]},"abstract":"<jats:p> Krabbe's disease (KD) is a demyelinating disorder caused by the deficiency of lysosomal galactocerebrosi-dase (GALC), affecting both the central (CNS) and the peripheral nervous system (PNS). A current therapy, hematopoietic stem cell transplantation (HSCT), is ineffective at correcting the PNS pathology. We have previously shown that systemic delivery of immortalized bone marrow-derived murine mesenchymal stromal cells (BM-MSCs) diminishes the neuropathology of transplanted Twitcher mice, a murine model of KD. In this study, to move one step closer to clinical application, the effectiveness of a systematic delivery of primary BM-MSCs to promote recovery of the Twitcher PNS was assessed. Primary BM-MSCsgrafted to the Twitcher sciatic nerve led to increased GALC activity that was not correlated to decreased psychosine (the toxic GALC substrate) accumulation. Nevertheless, BM-MSC transplantation rescued the axonal phenotype of Twitcher mice in the sciatic nerve, with an increased density of both myelinated and unmyelinated axons in transplanted animals. Whereas no increase in myelination was observed, upon transplantation an increased proliferation of Schwann cell precursors occurred. Supporting these findings, in vitro, BM-MSCs promoted neurite outgrowth of Twitcher sensory neurons and proliferation of Twitcher Schwann cells. Moreover, BM-MSCs expressed nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) and promoted increased BDNF synthesis by neighboring Schwann cells. Besides their action in neurons and glia, BM-MSCs led to macrophage activation in Twitcher sciatic nerves. In summary, primary BM-MSCs diminish the neuropathology of Twitcher sciatic nerves by coordinately affecting neurons, glia, and macrophages. <\/jats:p>","DOI":"10.3727\/096368913x669752","type":"journal-article","created":{"date-parts":[[2013,7,12]],"date-time":"2013-07-12T15:00:00Z","timestamp":1373641200000},"page":"239-252","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":8,"title":["Primary Bone Marrow Mesenchymal Stromal Cells Rescue the Axonal Phenotype of Twitcher Mice"],"prefix":"10.1177","volume":"23","author":[{"given":"Catarina Oliveira","family":"Miranda","sequence":"first","affiliation":[{"name":"Nerve Regeneration Group, Instituto de Biologia Molecular e Celular (IBMC), Porto, Portugal"},{"name":"ICBAS, Universidade do Porto, Porto, Portugal"}]},{"given":"Carla Andreia","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Nerve Regeneration Group, Instituto de Biologia Molecular e Celular (IBMC), Porto, Portugal"}]},{"given":"Vera Filipe","family":"Sousa","sequence":"additional","affiliation":[{"name":"Nerve Regeneration Group, Instituto de Biologia Molecular e Celular (IBMC), Porto, Portugal"},{"name":"ICBAS, Universidade do Porto, Porto, Portugal"}]},{"given":"Telma Emanuela","family":"Santos","sequence":"additional","affiliation":[{"name":"Nerve Regeneration Group, Instituto de Biologia Molecular e Celular (IBMC), Porto, Portugal"}]},{"given":"M\u00e1rcia Almeida","family":"Liz","sequence":"additional","affiliation":[{"name":"Nerve Regeneration Group, Instituto de Biologia Molecular e Celular (IBMC), Porto, Portugal"}]},{"given":"Ana Maio","family":"Marques","sequence":"additional","affiliation":[{"name":"Nerve Regeneration Group, Instituto de Biologia Molecular e Celular (IBMC), Porto, Portugal"}]},{"given":"Perp\u00e9tua","family":"Pinto-Do-\u00d3","sequence":"additional","affiliation":[{"name":"Instituto de Engenharia Biom\u00e9dica (INEB), Universidade do Porto, Porto, Portugal"}]},{"given":"M\u00f3nica Mendes","family":"Sousa","sequence":"additional","affiliation":[{"name":"Nerve Regeneration Group, Instituto de Biologia Molecular e Celular (IBMC), Porto, Portugal"}]}],"member":"179","published-online":{"date-parts":[[2014,3,1]]},"reference":[{"issue":"4","key":"bibr1-096368913X669752","first-page":"861","volume":"92","author":"Bischoff A.","year":"1969","journal-title":"Ultrastructural and histochemical findings. 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