Creation of a Large Adipose Tissue Construct in Humans Using a Tissue-engineering Chamber: A Step Forward in the Clinical Application of Soft Tissue Engineering

Wayne A Morrison, Diego Marre, Damien Grinsell, Andrew Batty, Nicholas Trost, Andrea J O'Connor, Wayne A Morrison, Diego Marre, Damien Grinsell, Andrew Batty, Nicholas Trost, Andrea J O'Connor

Abstract

Tissue engineering is currently exploring new and exciting avenues for the repair of soft tissue and organ defects. Adipose tissue engineering using the tissue engineering chamber (TEC) model has yielded promising results in animals; however, to date, there have been no reports on the use of this device in humans. Five female post mastectomy patients ranging from 35 to 49years old were recruited and a pedicled thoracodorsal artery perforator fat flap ranging from 6 to 50ml was harvested, transposed onto the chest wall and covered by an acrylic perforated dome-shaped chamber ranging from 140 to 350cm(3). Magnetic resonance evaluation was performed at three and six months after chamber implantation. Chambers were removed at six months and samples were obtained for histological analysis. In one patient, newly formed tissue to a volume of 210ml was generated inside the chamber. One patient was unable to complete the trial and the other three failed to develop significant enlargement of the original fat flap, which, at the time of chamber explantation, was encased in a thick fibrous capsule. Our study provides evidence that generation of large well-vascularized tissue engineered constructs using the TEC is feasible in humans.

Keywords: Adipose; Adipose-derived stem cells; Chamber; Inflammation; Soft tissue reconstruction; Tissue engineering.

Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Figures

Fig. 1
Fig. 1
Chamber and surgical procedure. (A) Acrylic 210 cm3 chamber with notch on one side to allow for pedicle passage. (B) Preoperative markings of thoracodorsal artery perforators and TAP flap design in patient 2. Tissue expander in place post right mastectomy. (C) Harvested fat flap approximately 30 ml based on thoracodorsal system. (D) Flap transposed onto chest wall with dome shaped chamber placed on top.
Fig. 2
Fig. 2
Intraoperative view upon chamber removal of patient 2. The 210 ml space is entirely filled with tissue. (A) Oblique lateral view. (B) Frontal view.
Fig. 3
Fig. 3
Detail of tissue generated in patient 2 showing adipose tissue under fibrous capsule in the lateral aspect.
Fig. 4
Fig. 4
Patient 2 after chamber removal. (A) Immediate postoperative result. (B) Six months follow-up. Newly grown tissue remained stable and had softened to a “fat-like” consistency.
Fig. 5
Fig. 5
(A) Specimen excised from patient 3 after formalin fixation. Note that in spite of early chamber removal (7 weeks), approximately a four-fold increase in tissue volume is observed. (B) Histological analysis showing viable adipose tissue as demonstrated by perilipin staining.
Fig. 6
Fig. 6
Intraoperative view upon chamber removal of patient 4. After removing the chamber, the space was empty, being fluid filled only, and the fat flap was seen to be encased in a thick fibrotic capsule without signs of enlargement (A). After capsulectomy, a healthy normal-looking adipose tissue flap was observed (B).
Fig. 7
Fig. 7
Histological analysis of encased fat excised in patient 4. (A) Perilipin staining confirms viability of adipose tissue under the fibrous capsule. (B) CD31 staining shows adipocytes surrounding perfused blood vessels.

References

    1. Atala A., Bauer S.B., Soker S., Yoo J.J., Retik A.B. Tissue-engineered autologous bladders for patients needing cystoplasty. Lancet. 2006;367:1241–1246.
    1. Birchall M.A., Seifalian A.M. Tissue engineering's green shoots of disruptive innovation. Lancet. 2014;384:288–290.
    1. Brorson H. Adipose tissue in lymphedema: the ignorance of adipose tissue in lymphedema. Lymphology. 2004;37:175–177.
    1. Cao Y. Angiogenesis modulates adipogenesis and obesity. J. Clin. Invest. 2007;117:2362–2368.
    1. Croll T.I., O'Connor A.J., Stevens G.W., Cooper-White J.J. A blank slate? Layer-by-layer deposition of hyaluronic acid and chitosan onto various surfaces. Biomacromolecules. 2006;7:1610–1622.
    1. Cronin K.J., Messina A., Knight K.R., et al. New murine model of spontaneous autologous tissue engineering, combining an arteriovenous pedicle with matrix materials. Plast. Reconstr. Surg. 2004;113:260–269.
    1. D'Alimonte I., Lannutti A., Pipino C., et al. Wnt signaling behaves as a “master regulator” in the osteogenic and adipogenic commitment of human amniotic fluid mesenchymal stem cells. Stem Cell Rev. 2013;9:642–654.
    1. DiEgidio P., Friedman H.I., Gourdie R.G., Riley A.E., Yost M.J., Goodwin R.L. Biomedical implant capsule formation: lessons learned and the road ahead. Ann. Plast. Surg. 2014;73:451–460.
    1. Dolderer J.H., Abberton K.M., Thompson E.W., et al. Spontaneous large volume adipose tissue generation from a vascularized pedicled fat flap inside a chamber space. Tissue Eng. 2007;13:673–681.
    1. Dolderer J.H., Thompson E.W., Slavin J., et al. Long-term stability of adipose tissue generated from a vascularized pedicled fat flap inside a chamber. Plast. Reconstr. Surg. 2011;127:2283–2292.
    1. Findlay M.W., Dolderer J.H., Trost N., et al. Tissue-engineered breast reconstruction: bridging the gap toward large-volume tissue engineering in humans. Plast. Reconstr. Surg. 2011;128:1206–1215.
    1. Forster N., Palmer J.A., Yeoh G., et al. Expansion and hepatocytic differentiation of liver progenitor cells in vivo using a vascularized tissue engineering chamber in mice. Tissue Eng. Part C Methods. 2011;17:359–366.
    1. Fulco I., Miot S., Haug M.D., et al. Engineered autologous cartilage tissue for nasal reconstruction after tumour resection: an observational first-in-human trial. Lancet. 2014;384:337–346.
    1. Go D.P., Palmer J.A., Mitchell G., Gras S.L., O'Connor A.J. Porous PLGA microspheres for dual delivery of biomolecules via the layer-by-layer assembly technique. J. Biomed. Mater. Res. A. 2015;103:1849–1863.
    1. Heit Y.I., Lancerotto L., Mesteri I., et al. External volume expansion increases subcutaneous thickness, cell proliferation, and vascular remodeling in a murine model. Plast. Reconstr. Surg. 2012;130:541–547.
    1. Henkel J., Woodruff M.A., Epari D.R., et al. Bone regeneration based on tissue engineering conceptions — a 21st century perspective. Bone Res. 2013;1:216–248.
    1. Huang C., Leavitt T., Bayer L.R., Orgill D.P. Effect of negative pressure wound therapy on wound healing. Curr. Probl. Surg. 2014;51:301–331.
    1. Hutley L.J., Herington A.C., Shurety W., et al. Human adipose tissue endothelial cells promote preadipocyte proliferation. Am. J. Physiol. Endocrinol. Metab. 2001;281:E1037–E1044.
    1. Khouri R.K., Rigotti G., Cardoso E., Khouri R.K., Jr., Biggs T.M. Megavolume autologous fat transfer: part II. Practice and techniques. Plast. Reconstr. Surg. 2014;133:1369–1377.
    1. Khouri R.K., Rigotti G., Khouri R.K., Jr., et al. Tissue-engineered breast reconstruction with Brava-assisted fat grafting: a 7-year, 488-patient, multicenter experience. Plast. Reconstr. Surg. 2015;135:643–658.
    1. Kølle S.F., Fischer-Nielsen A., Mathiasen A.B., et al. Enrichment of autologous fat grafts with ex-vivo expanded adipose tissue-derived stem cells for graft survival: a randomised placebo-controlled trial. Lancet. 2013;382:1113–1120.
    1. Kwan H.Y., Fu X., Liu B., et al. Subcutaneous adipocytes promote melanoma cell growth by activating the Akt signaling pathway: role of palmitic acid. J. Biol. Chem. 2014;289:30525–30537.
    1. Lattanzio S., Santilli F., Liani R., et al. Circulating dickkopf-1 in diabetes mellitus: association with platelet activation and effects of improved metabolic control and low-dose aspirin. J. Am. Heart Assoc. 2014;3(4) doi: 10.1161/JAHA.114.001000. Jul 18. pii: e001000.
    1. Lilja H.E., Morrison W.A., Han X.L., et al. An adipoinductive role of inflammation in adipose tissue engineering: key factors in the early development of engineered soft tissues. Stem Cells Dev. 2013;22:1602–1613.
    1. Liu Y.S., Lee O.K. In search of the pivot point of mechanotransduction: mechanosensing of stem cells. Cell Transplant. 2014;23:1–11.
    1. Lokmic Z., Stillaert F., Morrison W.A., Thompson E.W., Mitchell G.M. An arteriovenous loop in a protected space generates a permanent, highly vascular, tissue-engineered construct. FASEB J. 2007;21:511–522.
    1. Lujan-Hernandez J., Lancerotto L., Nabzdyk C., et al. Induction of adipogenesis by external volume expansion. Plast. Reconstr. Surg. 2016;137:122–131.
    1. Mennie J.C., Mohanna P.N., O'Donoghue J.M., Rainsbury R., Cromwell D.A. Donor-site hernia repair in abdominal flap breast reconstruction: a population-based cohort study of 7929 patients. Plast. Reconstr. Surg. 2015;136:1–9.
    1. Mian R., Morrison W.A., Hurley J.V., et al. Formation of new tissue from an arteriovenous loop in the absence of added extracellular matrix. Tissue Eng. 2000;6:595–603.
    1. Morritt A.N., Bortolotto S.K., Dilley R.J., et al. Cardiac tissue engineering in an in vivo vascularized chamber. Circulation. 2007;115:353–360.
    1. Olausson M., Patil P.B., Kuna V.K., et al. Transplantation of an allogeneic vein bioengineered with autologous stem cells: a proof-of-concept study. Lancet. 2012;380:230–237.
    1. Pike S., Zhang P., Wei Z., et al. In vitro effects of tamoxifen on adipose-derived stem cells. Wound Repair Regen. 2015;23:728–736.
    1. Poon C.J., Pereira E., Cotta M.V., Sinha S., et al. Preparation of an adipogenic hydrogel from subcutaneous adipose tissue. Acta Biomater. 2013;9:5609–5620.
    1. Post M.J., Rahimi N., Caolo V. Update on vascularization in tissue engineering. Regen. Med. 2013;8:759–770.
    1. Raya-Rivera A.M., Esquiliano D., Fierro-Pastrana R. Tissue-engineered autologous vaginal organs in patients: a pilot cohort study. Lancet. 2014;384:329–336.
    1. Rophael J.A., Craft R.O., Palmer J.A., et al. Angiogenic growth factor synergism in a murine tissue engineering model of angiogenesis and adipogenesis. Am. J. Pathol. 2007;171:2048–2057.
    1. Ross S.E., Hemati N., Longo K.A., et al. Inhibition of adipogenesis by Wnt signaling. Science. 2000;289:950–953.
    1. Rowan B.G., Gimble J.M., Sheng M., et al. Human adipose tissue-derived stromal/stem cells promote migration and early metastasis of triple negative breast cancer xenografts. PLoS One. 2014;9
    1. Seach N., Mattesich M., Abberton K., et al. Vascularized tissue engineering mouse chamber model supports thymopoiesis of ectopic thymus tissue grafts. Tissue Eng. Part C Methods. 2010;16:543–551.
    1. Tanaka Y., Tsutsumi A., Crowe D.M., Tajima S., Morrison W.A. Generation of an autologous tissue (matrix) flap by combining an arteriovenous shunt loop with artificial skin in rats: preliminary report. Br. J. Plast. Surg. 2000;53:51–57.
    1. Ting A.C., Craft R.O., Palmer J.A., et al. The adipogenic potential of various extracellular matrices under the influence of an angiogenic growth factor combination in a mouse tissue engineering chamber. Acta Biomater. 2014;10:1907–1918.
    1. Wittmann K., Dietl S., Ludwig N., et al. Engineering vascularized adipose tissue using the stromal-vascular fraction and fibrin hydrogels. Tissue Eng. A. 2015;21:1343–1353.
    1. Xu F.T., Li H.M., Yin Q.S., et al. Human breast adipose-derived stem cells transfected with the stromal cell-derived factor-1 receptor CXCR4 exhibit enhanced viability in human autologous free fat grafts. Cell. Physiol. Biochem. 2014;34:2091–2104.
    1. Zhan W., Chang Q., Xiao X., et al. Self-synthesized extracellular matrix contributes to mature adipose tissue regeneration in a tissue engineering chamber. Wound Repair Regen. 2015;23:443–452. May-Jun.
    1. Zhou Y., Wang J., Li H., et al. Efficacy and safety of cell-assisted lipotransfer; a systematic review and meta-analysis. Plast. Reconstr. Surg. 2016;137:44e–57e.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi