Human iPSC-derived MSCs (iMSCs) from aged individuals acquire a rejuvenation signature
Abstract Background Primary mesenchymal stem cells (MSCs) are fraught with aging-related shortfalls. Human-induced pluripotent stem cell (iPSC)-derived MSCs (iMSCs) have been shown to be a useful clinically relevant source of MSCs that circumvent these aging-associated drawbacks. To date, the extent...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-03-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13287-019-1209-x |
| _version_ | 1818984072575188992 |
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| author | Lucas-Sebastian Spitzhorn Matthias Megges Wasco Wruck Md Shaifur Rahman Jörg Otte Özer Degistirici Roland Meisel Rüdiger Volker Sorg Richard O. C. Oreffo James Adjaye |
| author_facet | Lucas-Sebastian Spitzhorn Matthias Megges Wasco Wruck Md Shaifur Rahman Jörg Otte Özer Degistirici Roland Meisel Rüdiger Volker Sorg Richard O. C. Oreffo James Adjaye |
| author_sort | Lucas-Sebastian Spitzhorn |
| collection | DOAJ |
| description | Abstract Background Primary mesenchymal stem cells (MSCs) are fraught with aging-related shortfalls. Human-induced pluripotent stem cell (iPSC)-derived MSCs (iMSCs) have been shown to be a useful clinically relevant source of MSCs that circumvent these aging-associated drawbacks. To date, the extent of the retention of aging-hallmarks in iMSCs differentiated from iPSCs derived from elderly donors remains unclear. Methods Fetal femur-derived MSCs (fMSCs) and adult bone marrow MSCs (aMSCs) were isolated, corresponding iPSCs were generated, and iMSCs were differentiated from fMSC-iPSCs, from aMSC-iPSCs, and from human embryonic stem cells (ESCs) H1. In addition, typical MSC characterization such as cell surface marker expression, differentiation capacity, secretome profile, and trancriptome analysis were conducted for the three distinct iMSC preparations—fMSC-iMSCs, aMSC-iMSCs, and ESC-iMSCs. To verify these results, previously published data sets were used, and also, additional aMSCs and iMSCs were analyzed. Results fMSCs and aMSCs both express the typical MSC cell surface markers and can be differentiated into osteogenic, adipogenic, and chondrogenic lineages in vitro. However, the transcriptome analysis revealed overlapping and distinct gene expression patterns and showed that fMSCs express more genes in common with ESCs than with aMSCs. fMSC-iMSCs, aMSC-iMSCs, and ESC-iMSCs met the criteria set out for MSCs. Dendrogram analyses confirmed that the transcriptomes of all iMSCs clustered together with the parental MSCs and separated from the MSC-iPSCs and ESCs. iMSCs irrespective of donor age and cell type acquired a rejuvenation-associated gene signature, specifically, the expression of INHBE, DNMT3B, POU5F1P1, CDKN1C, and GCNT2 which are also expressed in pluripotent stem cells (iPSCs and ESC) but not in the parental aMSCs. iMSCs expressed more genes in common with fMSCs than with aMSCs. Independent real-time PCR comparing aMSCs, fMSCs, and iMSCs confirmed the differential expression of the rejuvenation (COX7A, EZA2, and TMEM119) and aging (CXADR and IGSF3) signatures. Importantly, in terms of regenerative medicine, iMSCs acquired a secretome (e.g., angiogenin, DKK-1, IL-8, PDGF-AA, osteopontin, SERPINE1, and VEGF) similar to that of fMSCs and aMSCs, thus highlighting their ability to act via paracrine signaling. Conclusions iMSCs irrespective of donor age and cell source acquire a rejuvenation gene signature. The iMSC concept could allow circumventing the drawbacks associated with the use of adult MSCs und thus provide a promising tool for use in various clinical settings in the future. |
| first_indexed | 2024-12-20T18:13:11Z |
| format | Article |
| id | doaj.art-11e99ea7f60340549c4e2efeea6238b7 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-20T18:13:11Z |
| publishDate | 2019-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-11e99ea7f60340549c4e2efeea6238b72022-12-21T19:30:26ZengBMCStem Cell Research & Therapy1757-65122019-03-0110111810.1186/s13287-019-1209-xHuman iPSC-derived MSCs (iMSCs) from aged individuals acquire a rejuvenation signatureLucas-Sebastian Spitzhorn0Matthias Megges1Wasco Wruck2Md Shaifur Rahman3Jörg Otte4Özer Degistirici5Roland Meisel6Rüdiger Volker Sorg7Richard O. C. Oreffo8James Adjaye9Institute for Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich Heine UniversityInstitute for Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich Heine UniversityInstitute for Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich Heine UniversityInstitute for Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich Heine UniversityInstitute for Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich Heine UniversityDivision of Paediatric Stem Cell Therapy, Clinic for Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Heinrich Heine UniversityDivision of Paediatric Stem Cell Therapy, Clinic for Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Heinrich Heine UniversityInstitute for Transplantation Diagnostics and Cell Therapeutics, Heinrich Heine University Hospital, MoorenstrBone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of SouthamptonInstitute for Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich Heine UniversityAbstract Background Primary mesenchymal stem cells (MSCs) are fraught with aging-related shortfalls. Human-induced pluripotent stem cell (iPSC)-derived MSCs (iMSCs) have been shown to be a useful clinically relevant source of MSCs that circumvent these aging-associated drawbacks. To date, the extent of the retention of aging-hallmarks in iMSCs differentiated from iPSCs derived from elderly donors remains unclear. Methods Fetal femur-derived MSCs (fMSCs) and adult bone marrow MSCs (aMSCs) were isolated, corresponding iPSCs were generated, and iMSCs were differentiated from fMSC-iPSCs, from aMSC-iPSCs, and from human embryonic stem cells (ESCs) H1. In addition, typical MSC characterization such as cell surface marker expression, differentiation capacity, secretome profile, and trancriptome analysis were conducted for the three distinct iMSC preparations—fMSC-iMSCs, aMSC-iMSCs, and ESC-iMSCs. To verify these results, previously published data sets were used, and also, additional aMSCs and iMSCs were analyzed. Results fMSCs and aMSCs both express the typical MSC cell surface markers and can be differentiated into osteogenic, adipogenic, and chondrogenic lineages in vitro. However, the transcriptome analysis revealed overlapping and distinct gene expression patterns and showed that fMSCs express more genes in common with ESCs than with aMSCs. fMSC-iMSCs, aMSC-iMSCs, and ESC-iMSCs met the criteria set out for MSCs. Dendrogram analyses confirmed that the transcriptomes of all iMSCs clustered together with the parental MSCs and separated from the MSC-iPSCs and ESCs. iMSCs irrespective of donor age and cell type acquired a rejuvenation-associated gene signature, specifically, the expression of INHBE, DNMT3B, POU5F1P1, CDKN1C, and GCNT2 which are also expressed in pluripotent stem cells (iPSCs and ESC) but not in the parental aMSCs. iMSCs expressed more genes in common with fMSCs than with aMSCs. Independent real-time PCR comparing aMSCs, fMSCs, and iMSCs confirmed the differential expression of the rejuvenation (COX7A, EZA2, and TMEM119) and aging (CXADR and IGSF3) signatures. Importantly, in terms of regenerative medicine, iMSCs acquired a secretome (e.g., angiogenin, DKK-1, IL-8, PDGF-AA, osteopontin, SERPINE1, and VEGF) similar to that of fMSCs and aMSCs, thus highlighting their ability to act via paracrine signaling. Conclusions iMSCs irrespective of donor age and cell source acquire a rejuvenation gene signature. The iMSC concept could allow circumventing the drawbacks associated with the use of adult MSCs und thus provide a promising tool for use in various clinical settings in the future.http://link.springer.com/article/10.1186/s13287-019-1209-xAged MSCFetal MSCsiPSCsiMSCsTranscriptomeSecretome |
| spellingShingle | Lucas-Sebastian Spitzhorn Matthias Megges Wasco Wruck Md Shaifur Rahman Jörg Otte Özer Degistirici Roland Meisel Rüdiger Volker Sorg Richard O. C. Oreffo James Adjaye Human iPSC-derived MSCs (iMSCs) from aged individuals acquire a rejuvenation signature Stem Cell Research & Therapy Aged MSC Fetal MSCs iPSCs iMSCs Transcriptome Secretome |
| title | Human iPSC-derived MSCs (iMSCs) from aged individuals acquire a rejuvenation signature |
| title_full | Human iPSC-derived MSCs (iMSCs) from aged individuals acquire a rejuvenation signature |
| title_fullStr | Human iPSC-derived MSCs (iMSCs) from aged individuals acquire a rejuvenation signature |
| title_full_unstemmed | Human iPSC-derived MSCs (iMSCs) from aged individuals acquire a rejuvenation signature |
| title_short | Human iPSC-derived MSCs (iMSCs) from aged individuals acquire a rejuvenation signature |
| title_sort | human ipsc derived mscs imscs from aged individuals acquire a rejuvenation signature |
| topic | Aged MSC Fetal MSCs iPSCs iMSCs Transcriptome Secretome |
| url | http://link.springer.com/article/10.1186/s13287-019-1209-x |
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