{"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}
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}
{"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}
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}
{"title":"SIRT6 Knockdown in Buffalo Fetal Fibroblasts Exacerbates Premature Senescence Caused by DNA and Telomere Damage.","authors":"Jingyuan Liang, Jiayu Cui, Juanru Cheng, Yu Pan, Ruimen Zhang, Sufang Yang, Lingxiu Zou","doi":"10.1089/cell.2023.0048","DOIUrl":"10.1089/cell.2023.0048","url":null,"abstract":"<p><p>As a gene with antiaging functions, sirtuin6 (<i>SIRT6</i>) belonging to the sirtuin family plays a vital role in DNA repair, telomerase function, and cellular senescence, as well as maintains epigenomic stability and promotes longevity. However, its role in cell senescence in large animals, such as buffaloes, remains unknown. Fibroblasts are commonly used for somatic reprogramming, and their physiological characteristics affect the efficiency of this process. We aimed to elucidate the role of <i>SIRT6</i> in cellular senescence and proliferation and analyze its effect on the biological function of buffalo fibroblasts to help improve the efficiency of buffalo somatic cell reprogramming. The expression of SIRT6 and related DNA damage was measured in buffalo fibroblasts obtained at different developmental stages (in the fetus and at 3 and 10 years of age), and the effect of SIRT6 knockdown on the senescence of buffalo fetal fibroblast was investigated. An inverse relationship was observed between SIRT6 expression and senescence in buffalo fibroblasts obtained from animals of various ages. This was accompanied by decreased cell growth, viability, and increased DNA damage. Short hairpin RNA-mediated SIRT6 knockdown accelerated the senescence of buffalo fetal fibroblasts. It blocked the cell cycle during <i>in vitro</i> cell culture, which further enhanced DNA damage, particularly with respect to the telomeres. Collectively, our findings suggest that SIRT6 expression was closely associated with buffalo senescence in fibroblasts. These findings serve as a foundation to better understand the cellular functions of <i>SIRT6</i> and also aid in selecting donor cells for buffalo somatic cell reprogramming.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":" ","pages":"277-287"},"PeriodicalIF":1.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41112255","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 : 2023-12-01Epub Date: 2023-11-16DOI: 10.1089/cell.2023.0084
Derek B Asserson
{"title":"Allogeneic Mesenchymal Stem Cells After <i>In Vivo</i> Transplantation: A Review.","authors":"Derek B Asserson","doi":"10.1089/cell.2023.0084","DOIUrl":"10.1089/cell.2023.0084","url":null,"abstract":"<p><p>Autologous mesenchymal stem cells (MSCs) are ideal for tissue regeneration because of their ability to circumvent host rejection, but their procurement and processing present logistical and time-sensitive challenges. Allogeneic MSCs provide an alternative cell-based therapy capable of positively affecting all human organ systems, and can be readily available. Extensive research has been conducted in the treatment of autoimmune, degenerative, and inflammatory diseases with such stem cells, and has demonstrated predominantly safe outcomes with minimal complications. Nevertheless, continued clinical trials are necessary to ascertain optimal harvest and transplant techniques.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":" ","pages":"264-276"},"PeriodicalIF":1.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136396570","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":"Low-Intensity Nanosecond Pulsed Electric Field Accelerates Osteogenic Transformation of Human Dermal Fibroblasts by Enhancing Cell Pluripotency.","authors":"Jingtian Lai, Zewei Wang, Haiying Zhou, Pengfei Li, Hui Lu, Tian Tu","doi":"10.1089/cell.2023.0059","DOIUrl":"10.1089/cell.2023.0059","url":null,"abstract":"<p><p>Autologous human fibroblasts have the potential to differentiate into the osteogenic lineage under specific conditions and can be utilized for bone regeneration. However, their efficiency is currently unsatisfactory. Recently, low-intensity nanosecond pulsed electric field (nsPEF) stimulation has been demonstrated to enhance cell pluripotency by activating epigenetic regulatory pathways. In this study, human dermal fibroblasts were exposed to different intensities of nsPEF to assess whether these exposures resulted in changes in proliferation rate, calcium salt deposition, and expression of differentiation-related markers in different experimental groups. The results showed a significant increase in cell proliferation, pluripotency, bone marker expression, and osteogenic differentiation efficiency when stimulating cells with 5 kV/cm of nsPEF. However, cell proliferation and differentiation significantly decreased at 25 kV/cm. Additionally, the proliferation and efficiency of osteogenic differentiation were reduced when the nsPEF intensity was increased to 50 kV/cm. Treatment with a 5 kV/cm of nsPEF led to increased and concentrated expression of Yes-Associated Protein (YAP) in the nucleus. These observations suggest that human dermal fibroblasts possess a heightened potential to differentiate into osteogenic cells when activated with nsPEF at 5 kV/cm. Consequently, the nsPEF strengthening strategy shows promise for fibroblast-based tissue-engineered bone repair research.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":" ","pages":"300-309"},"PeriodicalIF":1.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138443991","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":"Gene Regulatory Networks: Improving Inferences with Transfer Learning.","authors":"Marcelo Tigre Moura","doi":"10.1089/cell.2023.0095","DOIUrl":"10.1089/cell.2023.0095","url":null,"abstract":"<p><p>Deep transfer learning improves the inference of gene regulatory networks in human cells, reveals disease-associated genes, and identifies network-based druggable targets in human heart disease.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":"25 6","pages":"261-263"},"PeriodicalIF":1.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138884549","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}