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 mann for illustrasjonene. L.M. ble støttet av en Pilot Award fra Cornell klinisk og Translational Science Center og en ASRM forskning tilskudd. Forfatterne vil gjerne takke James lab medlemmer for kritisk lesning av manuskriptet.

Alle prosedyrer som involverer dyr fag er godkjent av institusjonelle Animal Care og bruk Committee (IACUC) på Weill Cornell Medical College. Alle xenotransplantation eksperimenter ved hjelp av eggstokkene vev ble utført i samsvar med relevante retningslinjer og regler. Menneskelig ovarian vev ble samlet inn fra pasienter planlagt for kjemoterapi eller strålebehandling for kreftbehandling eller tidligere benmarg transplantasjon. Institusjonelle review board (IRB) komiteen av Weill Cornell Medical College godkjent saml...

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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. 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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. 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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>

Her viser vi at co transplantasjon av exECs gir en betydelig fordel for eggstokkreft vev levedyktighet og funksjon etter xenograft i mus. Standarder for klinisk anvendelse av eggstokkene vev auto-transplantasjon for fertilitet bevaring er ikke sett og optimale parametere (størrelse, transplantasjon område, varigheten av pode, etc.) 32 , 33 , 34 for økt utvinning av follikulær fortsatt udefinert. Når auto-transplant...

Kreft er fortsatt blant de viktigste årsakene til dødsfall i den industrialiserte verden, men tiår med forskning har gitt vesentlig fremgang for de fleste typer kreft, og i noen tilfeller nesten doblet overlevelse priser1. Dessverre er chemotherapeutic agenter ofte gonadotoxic, tappe reserve av primordial follicles i eggstokkene og reduserer fruktbarheten2. Denne voksende befolkningen kan ha nytte av ulike metoder for fertilitet bevaring inkludert oocyte og/eller embryoet kryonisk bevaring, men pasienter som krever rask oppstart av kreft terapi og pre pubertale pasienter er kvalifisert for disse alternativene. Som et alternativ, har noen pasienter valgt å cryopreserve ovarian vev før foretaket kaloriforbrenning terapeutiske og utvinning og remisjon, auto-transplanting vev gjenopprette fruktbarhet3. Likevel, hittil pode overlevelse og follikulær utdataene etter auto-transplantasjon fortsatt relativt lav4, hovedsakelig på grunn av vev iskemi og hypoksi5,6,7. Til tross for utallige forsøk på å forbedre levedyktigheten til eggstokkene kortikale grafts bruker antioksidanter8,9, pro-angiogenic cytokiner10,11,12,1 3eller mekanisk manipulasjoner14, pode iskemi i en 5 til 7 dagers vinduet etter transplantasjon undergraver levedyktighet og overlevelse av pode7. For å løse dette, utviklet vi en cellen-basert strategi for å lette anastomose av verten og pode fartøy og dermed fremskynde reperfusion av eggstokkene vev.
I tillegg til iskemiske fornærmelse mot podet ovarian vev i vinduet etter transplantasjon, kan avbrudd i Inter follikulær signalering bidra til uttømming av bassenget15,16. Fordi eksogene endotelceller (ExECs) bidra til stabile og fungerende fartøy i utkanten av graftet, presenterer de en unik mulighet til å formidle en definert molekylær inngang til transplanterte vev. Som et bevis på prinsippet, var ExECs konstruert å uttrykke super fysiologiske nivåer av Anti-Mullerian hormon (AMH), medlem av transformere vekstfaktor beta (TGFβ) gruppe som har vist seg å begrense follikulær vekst17. Sammenligning av follikulær distribusjon i grafts co transplantert med kontroll og AMH-uttrykke celler bekrefter biological aktivitet og styrken på utvikling exECs.
I sammendraget, kan ved å forbedre pode levedyktighet og undertrykke tidlig mobilisering av follikulær bassenget, denne tilnærmingen øke produktiviteten til auto-transplanted ovarian vev i pasienter som gjennomgår fertilitet bevaring. Videre kan den ExEC-basert plattformen eksperimentelle avhør av molekylære regulatorer som har vært innblandet i follikulær utvikling.

<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

Infertilitet er en hyppig bivirkning av kjemoterapi og/eller strålebehandling og for noen pasienter, kryonisk bevaring av oocytes eller embryoer er ikke et alternativ. Som et alternativ, et økende antall disse pasientene velger å cryopreserve ovarian vev for autograft etter utvinning og tilgivelse. Til tross for forbedringer i resultatene blant pasienter som gjennomgår auto-transplantasjon av cryopreserved ovarian vev, fortsatt effektiv revaskularisering av podet vev en stor utfordring. Å redusere iskemi og dermed bedre resultater i pasienter som gjennomgår auto-transplantasjon, utviklet vi en vaskulær cellen-basert strategi for akselererende perfusjon av eggstokkene vev. Vi beskriver en metode for co transplantasjon av eksogene endotelceller (ExECs) med cryopreserved ovarian vev i en mus xenograft modell. Vi utvider denne tilnærmingen å ansette ExECs som har blitt utviklet for å uttrykke constitutively Anti-Mullerian hormon (AMH), dermed muliggjør vedvarende paracrine signalering innspill til eggstokkene grafts. Co transplantasjon med ExECs økt follikulær volum og forbedret Boas hårsekken utvikling, og AMH-uttrykke ExECs forfremmet oppbevaring av quiescent primordial follikler. Denne kombinerte strategi kan være et nyttig verktøy for begrensende iskemi og modulerende follikulær aktivisering i sammenheng fertilitet bevaring og/eller infertilitet generelt.

For å fastslå om co transplantasjon av ExECs gir en fordel til pasienter vev, var tinte ovarian kortikale strimler delt i like store stykker og engrafted bilateralt i immun kompromittert, hilsen scid gamma (NSG), mus. En side i en fibrin blodpropp alene (ingen ECs) og de andre inneholder ExECs (figur 1a), hver musen tjenestegjorde som sin egen kontroll. ExECs ble innhentet via isolering av primære endotelet fra menneskelige kontrollkabler og påfølgende b...

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

For noen pasienter er det eneste alternativet for fertilitet bevaring kryonisk bevaring av eggstokkene vev. Dessverre, forsinket revaskularisering undergraver follikulær levedyktighet. Her presenterer vi en protokoll for co transplantasjon menneskelig ovarian vev med endotelceller for utnyttelse som cellen-basert strategi kombinere akselerert perfusjon med en direkte paracrine levering av bioaktive molekyler.

Co transplantasjon av menneskelig Ovarian vev med konstruert endotelceller: en celle-basert strategi kombinere akselerert perfusjon med direkte Paracrine levering

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

Sensing of Barrier vevsdesintegrasjon med en organisk Elektrokjemisk Transistor

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

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

Tissue Engineering av Tumor stromal mikromiljøet med Søknad til Cancer Cell Invasion

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

Produksjon, karakterisering og potensielle bruk av en 3D Tissue-konstruert Menneskelig Esophageal slimhinnene Model

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

Levering av proteiner, peptider eller celle-ugjennomtrengelig små molekyler inn i levende celler ved inkubasjon med den Endosomolytic Reagens 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

Automatisert Sammentrekning Analysis of Human Engineered hjertevev for Cardiac Drug Safety Screening

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 vaskulære nettverk med en vev modell i en Microfluidic enhet

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 av primære nyre vev segmenter og innlemmelse med romanen stillaset-fri konstruksjon teknologi

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

En ny Tenorrhaphy sutur teknikk med vev konstruert kollagen graft å reparere store sene defekter

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

Tredimensjonale mønstre av konstruert biofilm med en gjør-det-selv-Bioprinter

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

Etablering single-Cell basert co-kulturer i en deterministisk måte med en Mikrovæskebasert chip

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