학술논문

Engineering transplantable human lymphatic and blood capillary networks in a porous scaffold.
Document Type
Academic Journal
Author
Kong AM; O'Brien Institute Department of St Vincent's Institute of Medical Research, Fitzroy, VIC, Australia.; Lim SY; O'Brien Institute Department of St Vincent's Institute of Medical Research, Fitzroy, VIC, Australia.; Department of Surgery at St Vincent's Hospital Melbourne, University of Melbourne, Fitzroy, VIC, Australia.; Drug Discovery Biology, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia.; National Heart Research Institute Singapore, National Heart Centre Singapore.; Palmer JA; O'Brien Institute Department of St Vincent's Institute of Medical Research, Fitzroy, VIC, Australia.; Centre for Eye Research Australia, East Melbourne, VIC, Australia.; Rixon A; Experimental Medical and Surgical Unit, St Vincent's Hospital Melbourne, Fitzroy, VIC, Australia.; Gerrand YW; O'Brien Institute Department of St Vincent's Institute of Medical Research, Fitzroy, VIC, Australia.; Yap KK; O'Brien Institute Department of St Vincent's Institute of Medical Research, Fitzroy, VIC, Australia.; Department of Surgery at St Vincent's Hospital Melbourne, University of Melbourne, Fitzroy, VIC, Australia.; Morrison WA; O'Brien Institute Department of St Vincent's Institute of Medical Research, Fitzroy, VIC, Australia.; Department of Surgery at St Vincent's Hospital Melbourne, University of Melbourne, Fitzroy, VIC, Australia.; Faculty of Health Sciences, Australian Catholic University, East Melbourne VIC, Australia.; Department of Plastic and Reconstructive Surgery, St Vincent's Hospital Melbourne, Fitzroy, VIC, Australia.; Mitchell GM; O'Brien Institute Department of St Vincent's Institute of Medical Research, Fitzroy, VIC, Australia.; Department of Surgery at St Vincent's Hospital Melbourne, University of Melbourne, Fitzroy, VIC, Australia.; Faculty of Health Sciences, Australian Catholic University, East Melbourne VIC, Australia.
Source
Publisher: Sage Country of Publication: England NLM ID: 101550131 Publication Model: eCollection Cited Medium: Print ISSN: 2041-7314 (Print) Linking ISSN: 20417314 NLM ISO Abbreviation: J Tissue Eng Subsets: PubMed not MEDLINE
Subject
Language
English
ISSN
2041-7314
Abstract
Due to a relative paucity of studies on human lymphatic assembly in vitro and subsequent in vivo transplantation, capillary formation and survival of primary human lymphatic (hLEC) and blood endothelial cells (hBEC) ± primary human vascular smooth muscle cells (hvSMC) were evaluated and compared in vitro and in vivo. hLEC ± hvSMC or hBEC ± hvSMC were seeded in a 3D porous scaffold in vitro, and capillary percent vascular volume (PVV) and vascular density (VD)/mm 2 assessed. Scaffolds were also transplanted into a sub-cutaneous rat wound with morphology/morphometry assessment. Initially hBEC formed a larger vessel network in vitro than hLEC, with interconnected capillaries evident at 2 days. Interconnected lymphatic capillaries were slower (3 days) to assemble. hLEC capillaries demonstrated a significant overall increase in PVV ( p = 0.0083) and VD ( p = 0.0039) in vitro when co-cultured with hvSMC. A similar increase did not occur for hBEC + hvSMC in vitro, but hBEC + hvSMC in vivo significantly increased PVV ( p = 0.0035) and VD ( p = 0.0087). Morphology/morphometry established that hLEC vessels maintained distinct cell markers, and demonstrated significantly increased individual vessel and network size, and longer survival than hBEC capillaries in vivo, and established inosculation with rat lymphatics, with evidence of lymphatic function. The porous polyurethane scaffold provided advantages to capillary network formation due to its large (300-600 μm diameter) interconnected pores, and sufficient stability to ensure successful surgical transplantation in vivo. Given their successful survival and function in vivo within the porous scaffold, in vitro assembled hLEC networks using this method are potentially applicable to clinical scenarios requiring replacement of dysfunctional or absent lymphatic networks.
Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
(© The Author(s) 2022.)