{"title":"Revitalizing the Aging Immune System Through Selective Stem Cell Targeting.","authors":"Anna Konturek-Ciesla, David Bryder","doi":"10.1089/cell.2024.0029","DOIUrl":"https://doi.org/10.1089/cell.2024.0029","url":null,"abstract":"<p><p>The interplay between aging and immune system deterioration presents a formidable challenge to human health, especially in the context of a globally aging population. Aging is associated with a decline in the body's ability to combat infections and an increased risk of various diseases, underlining the importance of rejuvenating the immune system as a strategy for promoting healthier aging. In issue 628 of Nature (2024), Ross et al. present a compelling study that introduces a novel strategy for rejuvenating the aged immune system (Ross et al., 2024). By using antibodies to selectively eliminate \"aberrant\" hematopoietic stem cells (HSCs), this research opens new avenues for addressing age-related immune deterioration.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":"26 3","pages":"93-95"},"PeriodicalIF":1.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141449810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cellular reprogrammingPub Date : 2024-04-01Epub Date: 2024-03-26DOI: 10.1089/cell.2024.0020
Luis G Palma, Anna Bigas
{"title":"Making Human Hematopoietic Stem Cells Without Transgenes.","authors":"Luis G Palma, Anna Bigas","doi":"10.1089/cell.2024.0020","DOIUrl":"10.1089/cell.2024.0020","url":null,"abstract":"<p><p>Creating hematopoietic stem cells (HSCs) capable of multilineage engraft while possessing the ability to self-renew stands as a pivotal achievement within the field of regenerative medicine. However, achieving the generation of these cells without transgene expression or teratoma formation has not been fully accomplished. In a recent publication featured in <i>Cell Stem Cell</i>, Piau et al. document the production of functional HSCs derived from human-induced pluripotent stem cells (hiPSCs). They achieved this through a one-step differentiation protocol that notably does not require any transgene expression. hiPSCs-derived HSCs can engraft and self-renew upon serial transplantation and they are able to reconstitute lymphoid, myeloid, and erythroid compartments. This study presents a promising system to further study human HSC ontogeny, and it might represent a crucial step to obtain HSCs.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":" ","pages":"43-45"},"PeriodicalIF":1.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140287066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cellular reprogrammingPub Date : 2024-02-01Epub Date: 2024-01-31DOI: 10.1089/cell.2023.0116
Celia Fernandez-Rial, Miguel Fidalgo
{"title":"Induction of Transient Morula-Like Cells in Mice Through STAT3 Activation.","authors":"Celia Fernandez-Rial, Miguel Fidalgo","doi":"10.1089/cell.2023.0116","DOIUrl":"10.1089/cell.2023.0116","url":null,"abstract":"<p><p>Developing <i>in vitro</i> cell models that faithfully replicate the molecular and functional traits of cells from the earliest stages of mammalian development presents a significant challenge. The strategic induction of signal transducer and activator of transcription 3 (STAT3) phosphorylation, coupled with carefully defined culture conditions, facilitates the efficient reprogramming of mouse pluripotent cells into a transient morula-like cell (MLC) state. The resulting MLCs closely mirror their <i>in vivo</i> counterparts, exhibiting not only molecular resemblance but also the ability to differentiate into both embryonic and extraembryonic lineages. This reprogramming approach provides valuable insights into controlled cellular fate choice and opens new opportunities for studying early developmental processes in a dish.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":" ","pages":"8-9"},"PeriodicalIF":1.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139650333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Partial Reprogramming as a Method for Regenerating Neural Tissues in Aged Organisms.","authors":"Ali Saber Sichani, Somayeh Khoddam, Shayan Shakeri, Zahra Tavakkoli, Arad Ranji Jafroodi, Reza Dabbaghipour, Mohsen Sisakht, Jafar Fallahi","doi":"10.1089/cell.2023.0123","DOIUrl":"10.1089/cell.2023.0123","url":null,"abstract":"<p><p>Aging causes numerous age-related diseases, leading the human species to death. Nevertheless, rejuvenating strategies based on cell epigenetic modifications are a possible approach to counteract disease progression while getting old. Cell reprogramming of adult somatic cells toward pluripotency ought to be a promising tool for age-related diseases. However, researchers do not have control over this process as cells lose their fate, and cause potential cancerous cells or unexpected cell phenotypes. Direct and partial reprogramming were introduced in recent years with distinctive applications. Although direct reprogramming makes cells lose their identity, it has various applications in regeneration medicine. Temporary and regulated <i>in vivo</i> overexpression of Yamanaka factors has been shown in several experimental contexts to be achievable and is used to rejuvenate mice models. This regeneration can be accomplished by altering the epigenetic adult cell signature to the signature of a younger cell. The greatest advantage of partial reprogramming is that this method does not allow cells to lose their identity when they are resetting their epigenetic clock. It is a regimen of short-term Oct3/4, Sox2, Klf4, and c-Myc expression <i>in vivo</i> that prevents full reprogramming to the pluripotent state and avoids both tumorigenesis and the presence of unwanted undifferentiated cells. We know that many neurological age-related diseases, such as Alzheimer's disease, stroke, dementia, and Parkinson's disease, are the main cause of death in the last decades of life. Therefore, scientists have a special tendency regarding neuroregeneration methods to increase human life expectancy.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":"26 1","pages":"10-23"},"PeriodicalIF":1.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139912126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Reprogramming Stars #14: Fast-Forwarding Cellular Reprogramming- An Interview with Dr. Mark Kotter.","authors":"Mark R Kotter, Carlos-Filipe Pereira","doi":"10.1089/cell.2024.29111.mk","DOIUrl":"10.1089/cell.2024.29111.mk","url":null,"abstract":"","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":"26 1","pages":"2-7"},"PeriodicalIF":1.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139912127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carolina Cano Macip, Rokib Hasan, Victoria Hoznek, Jihyun Kim, Yuancheng Ryan Lu, Louis E Metzger, Saumil Sethna, Noah Davidsohn
{"title":"Gene Therapy-Mediated Partial Reprogramming Extends Lifespan and Reverses Age-Related Changes in Aged Mice.","authors":"Carolina Cano Macip, Rokib Hasan, Victoria Hoznek, Jihyun Kim, Yuancheng Ryan Lu, Louis E Metzger, Saumil Sethna, Noah Davidsohn","doi":"10.1089/cell.2023.0072","DOIUrl":"10.1089/cell.2023.0072","url":null,"abstract":"<p><p>Aging is a complex progression of changes best characterized as the chronic dysregulation of cellular processes leading to deteriorated tissue and organ function. Although aging cannot currently be prevented, its impact on life- and healthspan in the elderly can potentially be minimized by interventions that aim to return these cellular processes to optimal function. Recent studies have demonstrated that partial reprogramming using the Yamanaka factors (or a subset; <i>OCT4</i>, <i>SOX2,</i> and <i>KLF4; OSK)</i> can reverse age-related changes <i>in vitro</i> and <i>in vivo</i>. However, it is still unknown whether the Yamanaka factors (or a subset) are capable of extending the lifespan of aged wild-type (WT) mice. In this study, we show that systemically delivered adeno-associated viruses, encoding an inducible OSK system, in 124-week-old male mice extend the median remaining lifespan by 109% over WT controls and enhance several health parameters. Importantly, we observed a significant improvement in frailty scores indicating that we were able to improve the healthspan along with increasing the lifespan. Furthermore, in human keratinocytes expressing exogenous OSK, we observed significant epigenetic markers of age reversal, suggesting a potential reregulation of genetic networks to a younger potentially healthier state. Together, these results may have important implications for the development of partial reprogramming interventions to reverse age-associated diseases in the elderly.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":"26 1","pages":"24-32"},"PeriodicalIF":1.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10909732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139912125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cellular reprogrammingPub Date : 2024-02-01Epub Date: 2024-01-23DOI: 10.1089/cell.2023.0076
Jenin V Cortez, Kylie Hardwicke, Christopher G Grupen, Muren Herrid, Zoltan Machaty, Gábor Vajta
{"title":"Cloned Foal Born from Postmortem-Obtained Ear Sample Refrigerated for 5 Days Before Fibroblast Isolation and Decontamination of the Infected Monolayer Culture.","authors":"Jenin V Cortez, Kylie Hardwicke, Christopher G Grupen, Muren Herrid, Zoltan Machaty, Gábor Vajta","doi":"10.1089/cell.2023.0076","DOIUrl":"10.1089/cell.2023.0076","url":null,"abstract":"<p><p>A 6-year-old mare, a valuable polo horse, died of complications following postcolic surgery. To preserve its genetics, ear skin samples were collected immediately after death and stored in an equine embryo transfer medium at 4°C for 5 days. After trypsin digestion, monolayer fibroblast cultures were established, but signs of massive bacterial infection were found in all of them. As an ultimate attempt for rescue, rigorously and repeatedly washed cells were individually cultured in all wells of four 96-well dishes. New monolayers were established from the few wells without contamination and used for somatic cell nuclear transfer. Four of the six Day 7 blastocysts derived from 14 reconstructed zygotes were transferred in four naturally cycling mares on Day 5 after ovulation. The embryo transfers resulted in 2 pregnancies, one from a fresh and one from a vitrified blastocyst. The vitrified embryo transfer resulted in a healthy offspring, now 21 months old, genetically and phenotypically identical to the somatic cell donor animal.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":" ","pages":"33-36"},"PeriodicalIF":1.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139542007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Karg, Y. Lu, Nasrin Refaian, James Cameron, Emma Hoffmann, Cindy Hoppe, Shintaro Shirahama, Madhura Shah, Drenushe Krasniqi, A. Krishnan, Maleeka Shrestha, Yinjie Guo, Jennifer M. Cermak, Michel Walthier, Kasia Broniowska, Sharon Rosenzweig-Lipson, M. Gregory-Ksander, David A. Sinclair, Bruce R. Ksander
{"title":"Sustained Vision Recovery by OSK Gene Therapy in a Mouse Model of Glaucoma","authors":"M. Karg, Y. Lu, Nasrin Refaian, James Cameron, Emma Hoffmann, Cindy Hoppe, Shintaro Shirahama, Madhura Shah, Drenushe Krasniqi, A. Krishnan, Maleeka Shrestha, Yinjie Guo, Jennifer M. Cermak, Michel Walthier, Kasia Broniowska, Sharon Rosenzweig-Lipson, M. Gregory-Ksander, David A. Sinclair, Bruce R. Ksander","doi":"10.1089/cell.2023.0074","DOIUrl":"https://doi.org/10.1089/cell.2023.0074","url":null,"abstract":"","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":"48 24","pages":""},"PeriodicalIF":1.6,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138592215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}