{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,22]],"date-time":"2026-02-22T02:29:46Z","timestamp":1771727386568,"version":"3.50.1"},"reference-count":139,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2019,7,12]],"date-time":"2019-07-12T00:00:00Z","timestamp":1562889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["POCI-01-0145-FEDER-031402"],"award-info":[{"award-number":["POCI-01-0145-FEDER-031402"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The normal bone regeneration process is a complex and coordinated series of events involving different cell types and molecules. However, this process is impaired in critical-size\/large bone defects, with non-unions or delayed unions remaining a major clinical problem. Novel strategies are needed to aid the current therapeutic approaches. Mesenchymal stem\/stromal cells (MSCs) are able to promote bone regeneration. Their beneficial effects can be improved by modulating the expression levels of specific genes with the purpose of stimulating MSC proliferation, osteogenic differentiation or their immunomodulatory capacity. In this context, the genetic engineering of MSCs is expected to further enhance their pro-regenerative properties and accelerate bone healing. Herein, we review the most promising molecular candidates (protein-coding and non-coding transcripts) and discuss the different methodologies to engineer and deliver MSCs, mainly focusing on in vivo animal studies. Considering the potential of the MSC secretome for bone repair, this topic has also been addressed. Furthermore, the promising results of clinical studies using MSC for bone regeneration are discussed. Finally, we debate the advantages and limitations of using MSCs, or genetically-engineered MSCs, and their potential as promoters of bone fracture regeneration\/repair.<\/jats:p>","DOI":"10.3390\/ijms20143430","type":"journal-article","created":{"date-parts":[[2019,7,12]],"date-time":"2019-07-12T11:49:38Z","timestamp":1562932178000},"page":"3430","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Genetically Engineered-MSC Therapies for Non-unions, Delayed Unions and Critical-size Bone Defects"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3229-3293","authenticated-orcid":false,"given":"Jaime","family":"Freitas","sequence":"first","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, University of Porto, 4200-465 Porto, Portugal"},{"name":"INEB\u2014Instituto de Engenharia Biom\u00e9dica, University of Porto, 4200-465 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8604-2978","authenticated-orcid":false,"given":"Susana Gomes","family":"Santos","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, University of Porto, 4200-465 Porto, Portugal"},{"name":"INEB\u2014Instituto de Engenharia Biom\u00e9dica, University of Porto, 4200-465 Porto, Portugal"},{"name":"ICBAS\u2014Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, University of Porto, 4200-465 Porto, Portugal"}]},{"given":"Raquel Madeira","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, University of Porto, 4200-465 Porto, Portugal"},{"name":"INEB\u2014Instituto de Engenharia Biom\u00e9dica, University of Porto, 4200-465 Porto, Portugal"}]},{"given":"Jos\u00e9 Henrique","family":"Teixeira","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, University of Porto, 4200-465 Porto, Portugal"},{"name":"INEB\u2014Instituto de Engenharia Biom\u00e9dica, University of Porto, 4200-465 Porto, Portugal"},{"name":"ICBAS\u2014Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, University of Porto, 4200-465 Porto, Portugal"}]},{"given":"M\u00e1rio Adolfo","family":"Barbosa","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, University of Porto, 4200-465 Porto, Portugal"},{"name":"INEB\u2014Instituto de Engenharia Biom\u00e9dica, University of Porto, 4200-465 Porto, Portugal"},{"name":"ICBAS\u2014Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, University of Porto, 4200-465 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2072-8587","authenticated-orcid":false,"given":"Maria In\u00eas","family":"Almeida","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, University of Porto, 4200-465 Porto, Portugal"},{"name":"INEB\u2014Instituto de Engenharia Biom\u00e9dica, University of Porto, 4200-465 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2019,7,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.molmed.2009.07.002","article-title":"Mechanisms of bone repair and regeneration","volume":"15","author":"Deschaseaux","year":"2009","journal-title":"Trends Mol. 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