Name: co-transplantation of human ovarian tissue with engineered endothelial cells: a cell-based strategy combining accelerated perfusion with direct paracrine delivery
Uploaded: 2018-05-16T14:00:00
Description: Watch this Scientific Journal Video about Co-transplantation of Human Ovarian Tissue with Engineered Endothelial Cells: A Cell-based Strategy Combining Accelerated Perfusion with Direct Paracrine Deli

Omar Alexander Man para as ilustrações. L.M. foi apoiado por um prêmio de piloto da clínica Cornell e concessão de pesquisa Translational Science Center e um ASRM. Os autores gostaria de agradecer aos membros do laboratório James para uma leitura crítica do manuscrito.

Todos os procedimentos envolvendo assuntos animais foram aprovados pelo cuidado institucional do Animal e Comissão de utilização (IACUC) no Weill Cornell Medical College. Todos os experimentos xenotransplante usando tecido ovariano foram realizados em conformidade com os regulamentos e orientações pertinentes. Tecido ovariano humano foi coletado de pacientes agendados para quimioterapia ou radioterapia para tratamento de câncer ou transplante de medula de óssea prévia. O Conselho de revisão institucional (IRB) C...

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	<li>Siegel, R. L., Miller, K. D., Jemal, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cancer+Statistics,+2017.">Cancer Statistics, 2017.</a> CA Cancer J Clin. 67 (1), 7-30 (2017).</li><li>Magelssen, H., Melve, K. K., Skjaerven, R., Fossa, S. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Parenthood+probability+and+pregnancy+outcome+in+patients+with+a+cancer+diagnosis+during+adolescence+and+young+adulthood.">Parenthood probability and pregnancy outcome in patients with a cancer diagnosis during adolescence and young adulthood.</a> Hum Reprod. 23 (1), 178-186 (2008).</li><li>Donnez, J., Dolmans, M. M., Diaz, C., Pellicer, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ovarian+cortex+transplantation:+time+to+move+on+from+experimental+studies+to+open+clinical+application.">Ovarian cortex transplantation: time to move on from experimental studies to open clinical application.</a> Fertil Steril. 104 (5), 1097-1098 (2015).</li><li>Stoop, D., Cobo, A., Silber, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fertility+preservation+for+age-related+fertility+decline.">Fertility preservation for age-related fertility decline.</a> Lancet. 384 (9950), 1311-1319 (2014).</li><li>Aubard, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Orthotopic+and+heterotopic+autografts+of+frozen-thawed+ovarian+cortex+in+sheep.">Orthotopic and heterotopic autografts of frozen-thawed ovarian cortex in sheep.</a> Hum Reprod. 14 (8), 2149-2154 (1999).</li><li>Newton, H., Aubard, Y., Rutherford, A., Sharma, V., Gosden, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Low+temperature+storage+and+grafting+of+human+ovarian+tissue.">Low temperature storage and grafting of human ovarian tissue.</a> Hum Reprod. 11 (7), 1487-1491 (1996).</li><li>Van Eyck, A. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Electron+paramagnetic+resonance+as+a+tool+to+evaluate+human+ovarian+tissue+reoxygenation+after+xenografting.">Electron paramagnetic resonance as a tool to evaluate human ovarian tissue reoxygenation after xenografting.</a> Fertil Steril. 92 (1), 374-381 (2009).</li><li>Nugent, D., Newton, H., Gallivan, L., Gosden, R. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Protective+effect+of+vitamin+E+on+ischaemia-reperfusion+injury+in+ovarian+grafts.">Protective effect of vitamin E on ischaemia-reperfusion injury in ovarian grafts.</a> J Reprod Fertil. 114 (2), 341-346 (1998).</li><li>Kim, S. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Quantitative+assessment+of+ischemic+tissue+damage+in+ovarian+cortical+tissue+with+or+without+antioxidant+(ascorbic+acid)+treatment.">Quantitative assessment of ischemic tissue damage in ovarian cortical tissue with or without antioxidant (ascorbic acid) treatment.</a> Fertil Steril. 82 (3), 679-685 (2004).</li><li>Abir, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Improving+posttransplantation+survival+of+human+ovarian+tissue+by+treating+the+host+and+graft.">Improving posttransplantation survival of human ovarian tissue by treating the host and graft.</a> Fertil Steril. 95 (4), 1205-1210 (2011).</li><li>Friedman, O., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Possible+improvements+in+human+ovarian+grafting+by+various+host+and+graft+treatments.">Possible improvements in human ovarian grafting by various host and graft treatments.</a> Hum Reprod. 27 (2), 474-482 (2012).</li><li>Shikanov, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fibrin+encapsulation+and+vascular+endothelial+growth+factor+delivery+promotes+ovarian+graft+survival+in+mice.">Fibrin encapsulation and vascular endothelial growth factor delivery promotes ovarian graft survival in mice.</a> Tissue Eng Part A. 17 (23-24), 3095-3104 (2011).</li><li>Soleimani, R., Heytens, E., Oktay, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Enhancement+of+neoangiogenesis+and+follicle+survival+by+sphingosine-1-phosphate+in+human+ovarian+tissue+xenotransplants.">Enhancement of neoangiogenesis and follicle survival by sphingosine-1-phosphate in human ovarian tissue xenotransplants.</a> PLoS One. 6 (4), e19475 (2011).</li><li>Israely, T., Dafni, H., Nevo, N., Tsafriri, A., Neeman, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Angiogenesis+in+ectopic+ovarian+xenotransplantation:+multiparameter+characterization+of+the+neovasculature+by+dynamic+contrast-enhanced+MRI.">Angiogenesis in ectopic ovarian xenotransplantation: multiparameter characterization of the neovasculature by dynamic contrast-enhanced MRI.</a> Magn Reson Med. 52 (4), 741-750 (2004).</li><li>Buratini, J., Price, C. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Follicular+somatic+cell+factors+and+follicle+development.">Follicular somatic cell factors and follicle development.</a> Reprod Fertil Dev. 23 (1), 32-39 (2011).</li><li>Dunlop, C. E., Anderson, R. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+regulation+and+assessment+of+follicular+growth.">The regulation and assessment of follicular growth.</a> Scand J Clin Lab Invest Suppl. 244, 13-17 (2014).</li><li>Durlinger, A. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Control+of+primordial+follicle+recruitment+by+anti-M&#252;llerian+hormone+in+the+mouse+ovary.">Control of primordial follicle recruitment by anti-M&#252;llerian hormone in the mouse ovary.</a> Endocrinology. 140 (12), 5789-5796 (1999).</li><li>Schmidt, K. L., Ernst, E., Byskov, A. G., Nyboe Andersen, A., Yding Andersen, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Survival+of+primordial+follicles+following+prolonged+transportation+of+ovarian+tissue+prior+to+cryopreservation.">Survival of primordial follicles following prolonged transportation of ovarian tissue prior to cryopreservation.</a> Hum Reprod. 18 (12), 2654-2659 (2003).</li><li>Jensen, A. K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Outcomes+of+transplantations+of+cryopreserved+ovarian+tissue+to+41+women+in+Denmark.">Outcomes of transplantations of cryopreserved ovarian tissue to 41 women in Denmark.</a> Hum Reprod. 30 (12), 2838-2845 (2015).</li><li>Oktay, K., Newton, H., Aubard, Y., Salha, O., Gosden, R. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cryopreservation+of+immature+human+oocytes+and+ovarian+tissue:+an+emerging+technology?.">Cryopreservation of immature human oocytes and ovarian tissue: an emerging technology?.</a> Fertil Steril. 69 (1), 1-7 (1998).</li><li>Shultz, L. D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Human+lymphoid+and+myeloid+cell+development+in+NOD/LtSz-scid+IL2R+gamma+null+mice+engrafted+with+mobilized+human+hemopoietic+stem+cells.">Human lymphoid and myeloid cell development in NOD/LtSz-scid IL2R gamma null mice engrafted with mobilized human hemopoietic stem cells.</a> J Immunol. 174 (10), 6477-6489 (2005).</li><li>Ramalingam, R., Rafii, S., Worgall, S., Brough, D. E., Crystal, R. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=E1(-)E4(+)+adenoviral+gene+transfer+vectors+function+as+a+&amp;#34;pro-life&amp;#34;+signal+to+promote+survival+of+primary+human+endothelial+cells.">E1(-)E4(+) adenoviral gene transfer vectors function as a &amp;#34;pro-life&amp;#34; signal to promote survival of primary human endothelial cells.</a> Blood. 93 (9), 2936-2944 (1999).</li><li>Seandel, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Generation+of+a+functional+and+durable+vascular+niche+by+the+adenoviral+E4ORF1+gene.">Generation of a functional and durable vascular niche by the adenoviral E4ORF1 gene.</a> Proc Natl Acad Sci U S A. 105 (49), 19288-19293 (2008).</li><li>Meirow, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cortical+fibrosis+and+blood-vessels+damage+in+human+ovaries+exposed+to+chemotherapy.+Potential+mechanisms+of+ovarian+injury.">Cortical fibrosis and blood-vessels damage in human ovaries exposed to chemotherapy. Potential mechanisms of ovarian injury.</a> Hum Reprod. 22 (6), 1626-1633 (2007).</li><li>Assidi, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Identification+of+potential+markers+of+oocyte+competence+expressed+in+bovine+cumulus+cells+matured+with+follicle-stimulating+hormone+and/or+phorbol+myristate+acetate+in+vitro.">Identification of potential markers of oocyte competence expressed in bovine cumulus cells matured with follicle-stimulating hormone and/or phorbol myristate acetate in vitro.</a> Biol Reprod. 79 (2), 209-222 (2008).</li><li>Thakur, S. C., Datta, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Higher+expression+of+hyaluronan+binding+protein+1+(HABP1/p32/gC1qR/SF2)+during+follicular+development+and+cumulus+oocyte+complex+maturation+in+rat.">Higher expression of hyaluronan binding protein 1 (HABP1/p32/gC1qR/SF2) during follicular development and cumulus oocyte complex maturation in rat.</a> Mol Reprod Dev. 75 (3), 429-438 (2008).</li><li>Dolmans, M. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Short-term+transplantation+of+isolated+human+ovarian+follicles+and+cortical+tissue+into+nude+mice.">Short-term transplantation of isolated human ovarian follicles and cortical tissue into nude mice.</a> Reproduction. 134 (2), 253-262 (2007).</li><li>Amorim, C. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Impact+of+freezing+and+thawing+of+human+ovarian+tissue+on+follicular+growth+after+long-term+xenotransplantation.">Impact of freezing and thawing of human ovarian tissue on follicular growth after long-term xenotransplantation.</a> J Assist Reprod Genet. 28 (12), 1157-1165 (2011).</li><li>Kawamura, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hippo+signaling+disruption+and+Akt+stimulation+of+ovarian+follicles+for+infertility+treatment.">Hippo signaling disruption and Akt stimulation of ovarian follicles for infertility treatment.</a> Proc Natl Acad Sci U S A. 110 (43), 17474-17479 (2013).</li><li>Suzuki, N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Successful+fertility+preservation+following+ovarian+tissue+vitrification+in+patients+with+primary+ovarian+insufficiency.">Successful fertility preservation following ovarian tissue vitrification in patients with primary ovarian insufficiency.</a> Hum Reprod. 30 (3), 608-615 (2015).</li><li>Campbell, B. K., Clinton, M., Webb, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+role+of+anti-M&#252;llerian+hormone+(AMH)+during+follicle+development+in+a+monovulatory+species+(sheep).">The role of anti-M&#252;llerian hormone (AMH) during follicle development in a monovulatory species (sheep).</a> Endocrinology. 153 (9), 4533-4543 (2012).</li><li>Donnez, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Restoration+of+ovarian+activity+and+pregnancy+after+transplantation+of+cryopreserved+ovarian+tissue:+a+review+of+60+cases+of+reimplantation.">Restoration of ovarian activity and pregnancy after transplantation of cryopreserved ovarian tissue: a review of 60 cases of reimplantation.</a> Fertil Steril. 99 (6), 1503-1513 (2013).</li><li>Ferreira, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+effects+of+sample+size+on+the+outcome+of+ovarian+tissue+cryopreservation.">The effects of sample size on the outcome of ovarian tissue cryopreservation.</a> Reprod Domest Anim. 45 (1), 99-102 (2010).</li><li>Gavish, Z., Peer, G., Roness, H., Cohen, Y., Meirow, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Follicle+activation+and+'burn-out'+contribute+to+post-transplantation+follicle+loss+in+ovarian+tissue+grafts:+the+effect+of+graft+thickness.">Follicle activation and 'burn-out' contribute to post-transplantation follicle loss in ovarian tissue grafts: the effect of graft thickness.</a> Hum Reprod. 30 (4), 1003 (2015).</li><li>Donnez, J., Dolmans, M. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fertility+Preservation+in+Women.">Fertility Preservation in Women.</a> N Engl J Med. 377 (17), 1657-1665 (2017).</li><li>Salama, M., Woodruff, T. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=New+advances+in+ovarian+autotransplantation+to+restore+fertility+in+cancer+patients.">New advances in ovarian autotransplantation to restore fertility in cancer patients.</a> Cancer Metastasis Rev. 34 (4), 807-822 (2015).</li><li>Donnez, J., Dolmans, M. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ovarian+cortex+transplantation:+60+reported+live+births+brings+the+success+and+worldwide+expansion+of+the+technique+towards+routine+clinical+practice.">Ovarian cortex transplantation: 60 reported live births brings the success and worldwide expansion of the technique towards routine clinical practice.</a> J Assist Reprod Genet. 32 (8), 1167-1170 (2015).</li><li>Meirow, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transplantations+of+frozen-thawed+ovarian+tissue+demonstrate+high+reproductive+performance+and+the+need+to+revise+restrictive+criteria.">Transplantations of frozen-thawed ovarian tissue demonstrate high reproductive performance and the need to revise restrictive criteria.</a> Fertil Steril. 106 (2), 467-474 (2016).</li><li>Kalich-Philosoph, L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cyclophosphamide+triggers+follicle+activation+and+"burnout";+AS101+prevents+follicle+loss+and+preserves+fertility.">Cyclophosphamide triggers follicle activation and "burnout"; AS101 prevents follicle loss and preserves fertility.</a> Sci Transl Med. 5 (185), 185ra162 (2013).</li><li>Kano, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=AMH/MIS+as+a+contraceptive+that+protects+the+ovarian+reserve+during+chemotherapy.">AMH/MIS as a contraceptive that protects the ovarian reserve during chemotherapy.</a> Proc Natl Acad Sci U S A. 114 (9), E1688-E1697 (2017).</li></ol>

Aqui podemos demonstrar esse transplante co de executivos fornece um benefício significativo a viabilidade do tecido ovariano e função após enxerto heterólogo em camundongos. Normas para a aplicação clínica da autotransplante de tecido ovariano para preservação da fertilidade não foram conjunto e os parâmetros ideais (tamanho, local de transplante, duração do enxerto, etc.) 32 , 33 , 34 para recuperação ...

Câncer permanece entre as principais causas de morte no mundo desenvolvido, no entanto, décadas de pesquisa produziram um progresso significativo para a maioria dos tipos de câncer e em alguns casos quase duplicou de sobrevivência taxas1. Infelizmente, agentes quimioterapêuticos são frequentemente gonadotoxic, esgotando a reserva de folículos primordiais nos ovários e redução da fertilidade2. Este crescimento da população pode se beneficiar de vários métodos de preservação da fertilidade, incluindo criopreservação de ovócitos e/ou embrião, no entanto, pacientes que necessitam de iniciação rápida da terapia do câncer e pacientes pré-púberes são inelegíveis para essas opções. Como alternativa, alguns pacientes têm escolhido para cryopreserve tecido ovariano, antes de empreender o seu regime terapêutico e sobre recuperação e remissão, autotransplante de tecido para restaurar a fertilidade3. Ainda, até à data, sobrevivência do enxerto e folicular saída seguindo autotransplante permanecem relativamente baixos4, principalmente devido ao tecido isquemia e hipóxia5,6,7. Apesar de inúmeros esforços para melhorar a viabilidade do enxerto cortical ovariana usando anti-oxidantes8,9, pro-angiogênico citocinas10,11,12,1 3, ou manipulações mecânicas14, isquemia de enxerto em pós-transplante uma janela de 5 a 7 dia põe em causa a viabilidade e sobrevivência do enxerto7. Para resolver isso, nós desenvolvemos uma estratégia baseada em célula para facilitar a anastomose dos vasos host e enxerto e, portanto, apressar a reperfusão do tecido ovariano.
Além o insulto isquêmico ao tecido ovariano transplantado na janela pós-transplante, o rompimento de sinalização inter folicular pode contribuir ao esgotamento do pool15,16. Porque as células endoteliais exógenas (executivos) contribuem para navios estáveis e funcionando na periferia do enxerto, eles apresentam uma oportunidade única para transmitir uma entrada molecular definida para tecido transplantado. Como prova de princípio, os executivos foram projetados para níveis expressam super fisiológicos do hormônio Anti-Mulleriano (AMH), um membro da superfamília transformadora para a beta (TGFβ) fator de crescimento que tem sido mostrado para restringir o crescimento folicular17. Comparação da distribuição folicular em enxertos co transplantado com células AMH-expressando e controle verifica a atividade biológica e a potência de executivos de engenharia.
Em resumo, melhorando o enxerto viabilidade e suprimindo a mobilização precoce do pool folicular, esta abordagem pode aumentar a produtividade de autotransplante de tecido ovariano em pacientes submetidos à preservação da fertilidade. Além disso, a plataforma baseada em ExEC permite interrogatório experimental de reguladores moleculares que têm sido implicados no desenvolvimento folicular.

<table>
	<tbody>
		<tr>
			<td>Leibovitz&#8217;s L-15 medium</td>
			<td>Gibco</td>
			<td>11415064</td>
			<td></td>
		</tr>
		<tr>
			<td>Antibiotic-Antimycotic</td>
			<td>Gibco</td>
			<td>15240062</td>
			<td>Anti-Anti X100</td>
		</tr>
		<tr>
			<td>Sucrose</td>
			<td>Sigma</td>
			<td>S 1888</td>
			<td></td>
		</tr>
		<tr>
			<td>Fibrinogen</td>
			<td>Sigma</td>
			<td>F 8630</td>
			<td>from bovine plasma</td>
		</tr>
		<tr>
			<td>Thrombin</td>
			<td>Sigma</td>
			<td>T 1063</td>
			<td>from human plasma</td>
		</tr>
		<tr>
			<td>DMSO</td>
			<td>Sigma</td>
			<td>D 2650</td>
			<td></td>
		</tr>
		<tr>
			<td>DMEM</td>
			<td>Gibco</td>
			<td>12491015</td>
			<td></td>
		</tr>
		<tr>
			<td>Enzyme Cell Detachment Medium</td>
			<td>Invitrogen</td>
			<td>00-4555-56</td>
			<td>Accutase</td>
		</tr>
		<tr>
			<td>Plastic paraffin film</td>
			<td>Bemis NA</td>
			<td></td>
			<td>Parafilm M</td>
		</tr>
		<tr>
			<td>Surgical paper tape 2.5 cm</td>
			<td>3M</td>
			<td>1530-1</td>
			<td>Micropore</td>
		</tr>
		<tr>
			<td>Surgical Paper tape 1.25 cm</td>
			<td>3M</td>
			<td>1530-0</td>
			<td>Micropore</td>
		</tr>
		<tr>
			<td>Perforated plastic Surgical tape 1.25 cm</td>
			<td>3M</td>
			<td>1527-0</td>
			<td>Transpore</td>
		</tr>
		<tr>
			<td>Monofilament Absorbable Suture</td>
			<td>Covidien</td>
			<td>UM-203</td>
			<td>Biosyn</td>
		</tr>
		<tr>
			<td>Braided Absorbable Suture</td>
			<td>Covidien</td>
			<td>GL-889</td>
			<td>Polysorb</td>
		</tr>
		<tr>
			<td>Povidone-iodine Solution USP 10%</td>
			<td>Purdue Products</td>
			<td>67618-153-01</td>
			<td>Betadine Solution Swab Stick</td>
		</tr>
		<tr>
			<td>Cryoviales</td>
			<td>Nunc</td>
			<td>377267</td>
			<td>CryoTube</td>
		</tr>
		<tr>
			<td>sterile ocular lubricant</td>
			<td>Dechra</td>
			<td>17033-211-38</td>
			<td>Puralube</td>
		</tr>
		<tr>
			<td>1.7 ml micro-centrifuge tube</td>
			<td>Denville</td>
			<td>C-2172</td>
			<td>Eppendorf</td>
		</tr>
		<tr>
			<td>Anasthesia system</td>
			<td>VetEquip</td>
			<td>V-1 table top system with scavenging</td>
			<td></td>
		</tr>
		<tr>
			<td>Endothelial cells</td>
			<td>Angiocrine Biosciences, Inc., San Diego, CA, USA</td>
			<td></td>
			<td>Isolated, transfected with E4-ORF- 1 and labeled endothelial cells</td>
		</tr>
		<tr>
			<td>Trichrome stain</td>
			<td>Sigma</td>
			<td>HT15-1kt</td>
			<td>Trichrome Stain (Masson) Kit</td>
		</tr>
		<tr>
			<td>Isolectin</td>
			<td>Invitrogen</td>
			<td>I32450</td>
			<td>isolectin GS-IB4 From Griffonia simplicifolia, Alexa Fluor&#8482; 647 Conjugate</td>
		</tr>
	</tbody>
</table>

co-transplantation of human ovarian tissue with engineered endothelial cells: a cell-based strategy combining accelerated perfusion with direct paracrine delivery

Infertilidade é um efeito colateral frequente da quimioterapia e/ou radioterapia e para alguns pacientes, criopreservação de oócitos ou embriões não é uma opção. Como alternativa, um número crescente destes pacientes está optando por cryopreserve tecido ovariano para autoenxerto após recuperação e remissão. Apesar das melhorias em termos de resultados entre os pacientes submetidos a autotransplante de tecido ovariano criopreservado, revascularização eficiente do tecido enxertado continua a ser um grande obstáculo. Para atenuar a isquemia e, assim, melhorar os resultados em pacientes submetidos a autotransplante, desenvolvemos uma estratégia baseada em célula vascular para acelerar a perfusão do tecido ovariano. Nós descrevemos um método para co transplante de células endoteliais exógenas (executivos) com tecido ovariano criopreservado em um modelo de enxerto heterólogo do rato. Estendemos essa abordagem para empregar os executivos que têm sido projetados para expressar constitutivamente hormônio Anti-Mulleriano (AMH), permitindo assim sustentada parácrina sinalizando a entrada para enxertos ovarianos. Transplante co com executivos aumentou volume folicular e desenvolvimento folicular antral melhorada e AMH-expressando executivos promovido retenção dos folículos primordiais quiescentes. Essa estratégia combinada pode ser uma ferramenta útil para atenuar a isquemia e modulando a ativação folicular no contexto da preservação da fertilidade e/ou infertilidade em geral.

Para determinar se o transplante co de executivos fornece um benefício ao tecido dos pacientes, descongeladas tiras corticais ovarianos foram divididas em pedaços de tamanhos iguais e incorporadas bilateralmente em imuno-comprometido, NOD scid gama (NSG), ratos. Com um lado incorporado em um coágulo de fibrina sozinho (sem ECs) e os outros executivos contendo (Figura 1a), cada rato serviu como seu próprio controle. Os executivos foram obtidos através do ...

Watch this Scientific Journal Video about Co-transplantation of Human Ovarian Tissue with Engineered Endothelial Cells: A Cell-based Strategy Combining Accelerated Perfusion with Direct Paracrine Deli

Co-transplantation of Human Ovarian Tissue with Engineered Endothelial Cells: A Cell-based Strategy Combining Accelerated Perfusion with Direct Paracrine Delivery

Para alguns pacientes, a única opção para preservação de fertilidade é a criopreservação de tecido ovariano. Infelizmente, revascularização atrasada prejudica a viabilidade folicular. Aqui, apresentamos um protocolo para co transplante de tecido ovariano humano com células endoteliais para utilização como uma estratégia baseada em célula combinando acelerada perfusão com uma entrega parácrina direto de moléculas bioativas.

Co transplante de tecido ovariano humano com células endoteliais engenharia: uma combinação de estratégia baseada em célula acelerado perfusão com entrega direta parácrina

Infertility is a frequent side effect of chemotherapy and/or radiotherapy and for some patients, cryopreservation of oocytes or embryos is not an option. ...

Research

JoVE Journal

Bioengineering

Sensing of Barrier Tissue Disruption with an Organic Electrochemical Transistor

Sensoriamento de Barreira rompimento do tecido com um transistor Eletroquímica Orgânica

The gastrointestinal tract is an example of barrier tissue that provides a physical barrier against entry of pathogens and toxins, while allowing the ...

Bioengenharia

Tissue Engineering of Tumor Stromal Microenvironment with Application to Cancer Cell Invasion

Engenharia de Tecidos de tumor estromal Microenvironment com Aplicação a invasão Cancer Cell

3D organotypic cultures of epithelial cells on a matrix embedded with mesenchymal cells are widely used to study epithelial cell differentiation and ...

Production, Characterization and Potential Uses of a 3D Tissue-engineered Human Esophageal Mucosal Model

Produção, Caracterização e usos potenciais de uma mucosa esofágica Modelo 3D Human Tissue-engenharia

The incidence of both esophageal adenocarcinoma and its precursor, Barrett&#8217;s Metaplasia, are rising rapidly in the western world. Furthermore ...

Delivery of Proteins, Peptides or Cell-impermeable Small Molecules into Live Cells by Incubation with the Endosomolytic Reagent dfTAT

Entrega de proteínas, peptídeos ou célula-impermeável Pequenas moléculas em células vivas por incubação com o Endosomolytic Reagente dfTAT

Macromolecular delivery strategies typically utilize the endocytic pathway as a route of cellular entry. However, endosomal entrapment severely limits the ...

Automated Contraction Analysis of Human Engineered Heart Tissue for Cardiac Drug Safety Screening

Automated Análise contração do Coração Humano engenharia de tecidos para Screening Cardiac Drug Safety

Cardiac tissue engineering describes techniques to constitute three dimensional force-generating engineered tissues. For the implementation of these ...

Perfusable Vascular Network with a Tissue Model in a Microfluidic Device

Perfusable rede Vascular com um modelo de tecido em um dispositivo Microfluidic

A spheroid (a multicellular aggregate) is regarded as a good model of living tissues in the human body. Despite the significant advancement in the ...

Microdissection of Primary Renal Tissue Segments and Incorporation with Novel Scaffold-free Construct Technology

Microdissection de segmentos de tecido Renal primária e incorporação com tecnologia de construção romance livre de andaime

Kidney transplantation is now a mainstream therapy for end-stage renal disease. However, with approximately 96,000 people on the waiting list and only ...

A Novel Tenorrhaphy Suture Technique with Tissue Engineered Collagen Graft to Repair Large Tendon Defects

Uma nova técnica de sutura tenorrhaphy com enxerto de colágeno projetado por tecido para reparar defeitos grandes do tendão

Surgical management of large tendon defects with tendon grafts is challenging, as there are a finite number of sites where donors can be readily ...

Three-dimensional Patterning of Engineered Biofilms with a Do-it-yourself Bioprinter

Padronização tridimensional de biofilmes projetados com uma Bioimpressora do-it-yourself

Biofilms are aggregates of bacteria embedded in a self-produced spatially-patterned extracellular matrix. Bacteria within a biofilm develop enhanced ...

Establishing Single-Cell Based Co-Cultures in a Deterministic Manner with a Microfluidic Chip

Estabelecendo co-culturas baseadas em uma única célula de forma determinística com um chip Microfluídico

Cell co-culture assays have been widely used for studying cell-cell interactions between different cell types to better understand the biology of diseases ...