Cancer Stem Cell News
Cell Therapy News
Dermal Cell News
Endothelial Cell News
ESC & iPSC News
Extracellular Matrix News
Hematopoiesis News
Hepatic Cell News
Human Immunology News
Immune Regulation News
Intestinal Cell News
Mammary Cell News
Mesenchymal Cell News
Muscle Cell News
Neural Cell News
Organoid News
Pancreatic Cell News
Prostate Cell News
Pulmonary Cell NewsInvestigators report on a novel, simplified differentiation method for forming functional osteoclasts from hiPSCs.
[Journal of Bone and Mineral Research]
6606345 UV5WQ2P8 items 1 apa 0 default asc 1 161658 https://www.stemcellsciencenews.com/wp-content/plugins/zotpress/
%7B%22status%22%3A%22success%22%2C%22updateneeded%22%3Afalse%2C%22instance%22%3A%22zotpress-b6b7feb186e0b9390344059fbc27a306%22%2C%22meta%22%3A%7B%22request_last%22%3A0%2C%22request_next%22%3A0%2C%22used_cache%22%3Atrue%7D%2C%22data%22%3A%5B%7B%22key%22%3A%22UV5WQ2P8%22%2C%22library%22%3A%7B%22id%22%3A6606345%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22R%5Cu00f6ssler%20et%20al.%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3ER%26%23xF6%3Bssler%2C%20U.%2C%20Hennig%2C%20A.%20F.%2C%20Stelzer%2C%20N.%2C%20Bose%2C%20S.%2C%20Kopp%2C%20J.%2C%20S%26%23xF8%3Be%2C%20K.%2C%20Cyganek%2C%20L.%2C%20Zifarelli%2C%20G.%2C%20Ali%2C%20S.%2C%20Hagen%2C%20M.%20von%20der%2C%20Str%26%23xE4%3Bssler%2C%20E.%2C%20Hahn%2C%20G.%2C%20Pusch%2C%20M.%2C%20Stauber%2C%20T.%2C%20Izsv%26%23xE1%3Bk%2C%20Z.%2C%20Gossen%2C%20M.%2C%20Stachelscheid%2C%20H.%2C%20%26amp%3B%20Kornak%2C%20U.%20%28n.d.%29.%20Efficient%20generation%20of%20osteoclasts%20from%20human%20induced%20pluripotent%20stem%20cells%20and%20functional%20investigations%20of%20lethal%20CLCN7-related%20osteopetrosis.%20%3Ci%3EJournal%20of%20Bone%20and%20Mineral%20Research%3C%5C%2Fi%3E%2C%20%3Ci%3En%5C%2Fa%3C%5C%2Fi%3E%28n%5C%2Fa%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2Fhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1002%5C%2Fjbmr.4322%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2Fhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1002%5C%2Fjbmr.4322%3C%5C%2Fa%3E%20%3Ca%20title%3D%27Cite%20in%20RIS%20Format%27%20class%3D%27zp-CiteRIS%27%20href%3D%27https%3A%5C%2F%5C%2Fwww.stemcellsciencenews.com%5C%2Fwp-content%5C%2Fplugins%5C%2Fzotpress%5C%2Flib%5C%2Frequest%5C%2Frequest.cite.php%3Fapi_user_id%3D6606345%26amp%3Bitem_key%3DUV5WQ2P8%27%3ECite%3C%5C%2Fa%3E%20%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Efficient%20generation%20of%20osteoclasts%20from%20human%20induced%20pluripotent%20stem%20cells%20and%20functional%20investigations%20of%20lethal%20CLCN7-related%20osteopetrosis%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Uta%22%2C%22lastName%22%3A%22R%5Cu00f6ssler%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Anna%20Floriane%22%2C%22lastName%22%3A%22Hennig%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Nina%22%2C%22lastName%22%3A%22Stelzer%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Shroddha%22%2C%22lastName%22%3A%22Bose%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Johannes%22%2C%22lastName%22%3A%22Kopp%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Kent%22%2C%22lastName%22%3A%22S%5Cu00f8e%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Lukas%22%2C%22lastName%22%3A%22Cyganek%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Giovanni%22%2C%22lastName%22%3A%22Zifarelli%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Salaheddine%22%2C%22lastName%22%3A%22Ali%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Maja%20von%20der%22%2C%22lastName%22%3A%22Hagen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Elisabeth%22%2C%22lastName%22%3A%22Str%5Cu00e4ssler%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Gabriele%22%2C%22lastName%22%3A%22Hahn%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Michael%22%2C%22lastName%22%3A%22Pusch%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Tobias%22%2C%22lastName%22%3A%22Stauber%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Zsuzsanna%22%2C%22lastName%22%3A%22Izsv%5Cu00e1k%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Manfred%22%2C%22lastName%22%3A%22Gossen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Harald%22%2C%22lastName%22%3A%22Stachelscheid%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Uwe%22%2C%22lastName%22%3A%22Kornak%22%7D%5D%2C%22abstractNote%22%3A%22Human%20induced%20pluripotent%20stem%20cells%20%28hiPSCs%29%20hold%20great%20potential%20for%20modelling%20human%20diseases%20and%20the%20development%20of%20innovative%20therapeutic%20approaches.%20Here%2C%20we%20report%20on%20a%20novel%2C%20simplified%20differentiation%20method%20for%20forming%20functional%20osteoclasts%20from%20hiPSCs.%20The%20three-step%20protocol%20starts%20with%20embryoid%20body%20formation%2C%20followed%20by%20hematopoietic%20specification%2C%20and%20finally%20osteoclast%20differentiation.%20We%20observed%20continuous%20production%20of%20monocyte-like%20cells%20over%20a%20period%20of%20up%20to%20nine%20weeks%2C%20generating%20sufficient%20material%20for%20several%20osteoclast%20differentiations.%20The%20analysis%20of%20stage-specific%20gene%20and%20surface%20marker%20expression%20proved%20mesodermal%20priming%2C%20the%20presence%20of%20monocyte-like%20cells%2C%20and%20of%20terminally%20differentiated%20multinucleated%20osteoclasts%2C%20able%20to%20form%20resorption%20pits%20and%20trenches%20on%20bone%20and%20dentine%20in%20vitro.%20In%20comparison%20to%20peripheral%20blood%20mononuclear%20cell%20%28PBMC%29-derived%20osteoclasts%20hiPSC-derived%20osteoclasts%20were%20larger%20and%20contained%20a%20higher%20number%20of%20nuclei.%20Detailed%20functional%20studies%20on%20the%20resorption%20behaviour%20of%20hiPSC-osteoclasts%20indicated%20a%20trend%20towards%20forming%20more%20trenches%20than%20pits%20and%20an%20increase%20in%20pseudo-resorption.%20We%20used%20hiPSCs%20from%20an%20ARO%20patient%20%28BIHi002-A%2C%20ARO%20hiPSCs%29%20with%20compound%20heterozygous%20missense%20mutations%20p.%28G292E%29%20and%20p.%28R403Q%29%20in%20CLCN7%2C%20coding%20for%20the%20Cl-%5C%2FH%2B-exchanger%20ClC-7%2C%20for%20functional%20investigations.%20The%20patient%27s%20leading%20clinical%20feature%20was%20a%20brain%20malformation%20due%20to%20defective%20neuronal%20migration.%20Mutant%20ClC-7%20displayed%20residual%20expression%20and%20retained%20lysosomal%20co-localization%20with%20OSTM1%2C%20but%20only%20ClC-7%20harboring%20the%20mutation%20p.%28R403Q%29%20gave%20strongly%20reduced%20ion%20currents.%20An%20increased%20autophagic%20flux%20in%20spite%20of%20unchanged%20lysosomal%20pH%20was%20evident%20in%20undifferentiated%20ARO%20hiPSCs.%20ARO%20hiPSC-derived%20osteoclasts%20showed%20an%20increased%20size%20compared%20to%20hiPSCs%20of%20healthy%20donors.%20They%20were%20not%20able%20to%20resorb%20bone%2C%20indicating%20a%20loss-of-function%20effect%20of%20the%20mutations.%20In%20summary%2C%20we%20developed%20a%20highly%20reproducible%2C%20straightforward%20hiPSC-osteoclast%20differentiation%20protocol.%20We%20demonstrated%20that%20osteoclasts%20differentiated%20from%20ARO-hiPSCs%20can%20be%20used%20as%20a%20disease%20model%20for%20ARO%20and%20potentially%20also%20other%20osteoclast-related%20diseases.%20This%20article%20is%20protected%20by%20copyright.%20All%20rights%20reserved.%22%2C%22date%22%3A%22%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%22https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1002%5C%2Fjbmr.4322%22%2C%22ISSN%22%3A%221523-4681%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fasbmr.onlinelibrary.wiley.com%5C%2Fdoi%5C%2Fabs%5C%2F10.1002%5C%2Fjbmr.4322%22%2C%22collections%22%3A%5B%5D%2C%22dateModified%22%3A%222021-04-28T21%3A48%3A09Z%22%7D%7D%5D%7D
Rössler, U., Hennig, A. F., Stelzer, N., Bose, S., Kopp, J., Søe, K., Cyganek, L., Zifarelli, G., Ali, S., Hagen, M. von der, Strässler, E., Hahn, G., Pusch, M., Stauber, T., Izsvák, Z., Gossen, M., Stachelscheid, H., & Kornak, U. (n.d.). Efficient generation of osteoclasts from human induced pluripotent stem cells and functional investigations of lethal CLCN7-related osteopetrosis. Journal of Bone and Mineral Research, n/a(n/a). https://doi.org/https://doi.org/10.1002/jbmr.4322 Cite
