Stem Cell-Based Soft Tissue Grafts for Plastic and Reconstructive Surgeries

ABSTRACT

Adipose tissue is often a key structure to restore in reconstructive and augmentative surgeries. Current materials for soft tissue reconstruction or augmentation suffer from shortcomings such as suboptimal volume retention, donor site morbidity, and poor biocompatibility. A series of experiments are presented here to describe our stem cell-based approach to engineering human adipose tissue with predefined shape and dimensions. These findings indicate the real possibility that biologically viable adipose tissue can be engineered by taking a teaspoon full of tissue fluid containing the patient's adult stem cells, expanding them, differentiating them into adipogenic cells, and encapsulating them into appropriate biocompatible polymer materials. The end result is anticipated to be minimal donor site trauma related to needle size, immune compatibility because the patient's own stem cells are used, and long-term volume maintenance because stem cells are capable of replenishing adipogenic cells to retain the predefined shape and dimensions of the engineered soft tissue. Upcoming challenges include long-term volume maintenance, tissue maturation, angiogenesis, scaling up, and host tissue integration. Conceptually, stem cell-derived soft tissue grafts are realizable in plastic and reconstructive surgical procedures.

KEYWORDS

Stem cells - soft tissue - adipose tissue - tissue engineering - adipogenic

REFERENCES

• 1 Yaremchuk M J. Facial skeletal reconstruction using porous polyethylene implants.  Plast Reconstr Surg. 2003;  111 1818-1827
• 2 Coppit G L, Lin D T, Burkey B B. Current concepts in lip reconstruction.  Curr Opin Otolaryngol Head Neck Surg. 2004;  12 281-287
• 3 Vural E. Surgical reconstruction in patients with cancer of the head and neck.  Curr Oncol Rep. 2004;  6 133-140
• 4 Atala A. Future perspectives in reconstructive surgery using tissue engineering.  Urol Clin North Am. 1999;  26 157-168
• 5 Davis R E, Guida R A, Cook T A. Autologous free dermal fat graft. Reconstruction of facial contour defects.  Arch Otolaryngol Head Neck Surg. 1995;  121 95-100
• 6 Thaller S R, Zarem H A, Kawamoto H K. Surgical correction of late sequelae from facial bone fractures.  Am J Surg. 1987;  154 149-153
• 7 Roncevic R, Roncevic D. Extensive, traumatic fractures of the orbit in war and peace time.  J Craniofac Surg. 1999;  10 284-300
• 8 Peterson S L, Moore E E. The integral role of the plastic surgeon at a level I trauma center.  Plast Reconstr Surg. 2003;  112 1371-1375
• 9 Kaban L B, Padwa B L, Mulliken J B. Surgical correction of mandibular hypoplasia in hemifacial microsomia: the case for treatment in early childhood.  J Oral Maxillofac Surg. 1998;  56 628-638
• 10 Monahan R, Seder K, Patel P, Alder M, Grud S, O'Gara M. Hemifacial microsomia. Etiology, diagnosis and treatment.  J Am Dent Assoc. 2001;  132 1402-1408
• 11 American Society of Plastic Surgery . 2004 Statistics.  Available at: http://www.plasticsurgery.org/public_education/2004Statistics.cfm , Last accessed: August 10 2005; 
• 12 Billings E, May J. Historical review and present status of free fat graft autotransplantation in plastic and reconstructive surgery.  Plast Reconstr Surg. 1989;  83 368-381
• 13 Smaehel J, Meyer V, Shutz K. Vascular augmentation of free adipose tissue grafts.  Eur J Plast Surg. 1990;  13 163-168
• 14 Lee K Y, Halberstadt C R, Holder W D, Mooney D J. Breast reconstruction. In: Lanza RP, Langer R, Vacanti J Principles of Tissue Engineering. 2nd ed. San Diego, CA; Academic Press 2000: 409-423
• 15 Kononas T C, Bucky L P, Hurley C, Amy J W. The fate of suctioned and surgically removed fat after reimplantation for soft tissue augmentation: a volumetric and histologic study in the rabbit.  Plast Reconstr Surg. 1993;  91 763-768
• 16 von Heimburg D, Zachariah S, Heschel I et al.. Human preadipocytes seeded on freeze dried collagen scaffolds investigated in vitro and in vivo.  Biomaterials. 2001;  22 429-438
• 17 Patrick Jr C W, Chauvin P B, Hobley J, Reece G P. Preadipocyte seeded PLGA scaffolds for adipose tissue engineering.  Tissue Eng. 1999;  5 139-151
• 18 Miller M J, Patrick Jr C W. Tissue engineering.  Clin Plast Surg. 2003;  30 91-103
• 19 Fischbach C, Spruss T, Weiser B et al.. Generation of mature fat pads in vitro and in vivo utilizing 3-D long-term culture of 3T3-L1 preadipocytes.  Exp Cell Res. 2004;  300 54-64
• 20 Neels J G, Thinnes T, Loskutoff D J. Angiogenesis in an in vivo model of adipose tissue development.  FASEB J. 2004;  18 983-985
• 21 Halberstadt C, Austin C, Rowley J et al.. A hydrogel material for plastic and reconstructive applications injected into the subcutaneous space of a sheep.  Tissue Eng. 2002;  8 309-319
• 22 Toriyama K, Kawaguchi N, Kitoh J et al.. Endogenous adipocyte precursor cells for regenerative soft-tissue engineering.  Tissue Eng. 2002;  8 157-165
• 23 Kimura Y, Ozeki M, Inamoto T, Tabata Y. Adipose tissue engineering based on human preadipocytes combined with gelatin microspheres containing basic fibroblast growth factor.  Biomaterials. 2003;  24 2513-2521
• 24 Caplan A I. Mesenchymal stem cells.  J Orthop Res. 1991;  9 641-650
• 25 Pittenger M F, Mackay A M, Beck S C et al.. Multilineage potential of adult human mesenchymal stem cells.  Science. 1999;  284 143-147
• 26 Alhadlaq A, Mao J J. Mesenchymal stem cells: isolation and therapeutics.  Stem Cells Dev. 2004;  13 436-448
• 27 Alhadlaq A, Tang M, Mao J J. Engineered adipose tissue from human mesenchymal stem cells maintains predefined shape and dimension: implications in soft tissue augmentation and reconstruction.  Tissue Eng. 2005;  11 556-566
• 28 Mao J J. Stem cell driven regeneration of synovial joint.  Biol Cell. 2005;  97 289-301
• 29 Shin H, Temenoff J S, Bowden G C et al.. Osteogenic differentiation of rat bone marrow stromal cells cultured on Arg-Gly-Asp modified hydrogels without dexamethasone and beta-glycerol phosphate.  Biomaterials. 2005;  26 3645-3654
• 30 Friedenstein A J, Piatetzky-Shapiro I I, Petrakova K V. Osteogenesis in transplants of bone marrow cells.  J Embryol Exp Morphol. 1966;  16 381-390
• 31 Tremain N, Korkko J, Ibberson D. MicroSA analysis of 2,353 expressed genes in a single cell-derived colony of undifferentiated human mesenchymal stem cells reveals mRNAs of multiple cell lineages.  Stem Cells. 2001;  19 408-418
• 32 Langer R S, Vacanti J P. Tissue engineering: the challenges ahead.  Sci Am. 1999;  280 86-89
• 33 Brey E M, Patrick Jr C W. Tissue engineering applied to reconstructive surgery.  IEEE Eng Med Biol Mag. 2000;  15 122-125
• 34 Griffith L G, Naughton G. Tissue engineering-current challenges and expanding opportunities.  Science. 2002;  295 1009-1014
• 35 Garfein E S, Orgill D P, Pribaz J J. Clinical applications of tissue engineered constructs.  Clin Plast Surg. 2003;  30 485-498
• 36 Sekiya I, Larson B L, Vuoristo J T, Cui J G, Prockop D J. Adipogenic differentiation of human adult stem cells from bone marrow stroma (MSCs).  J Bone Miner Res. 2004;  19 256-264
• 37 Marler J J, Guha A, Rowley J et al.. Soft-tissue augmentation with injectable alginate and syngeneic fibroblasts.  Plast Reconstr Surg. 2000;  105 2049-2057
• 38 Bryant S J, Anseth K S. Controlling the spatial distribution of ECM components in degradable PEG hydrogels for tissue engineering cartilage.  J Biomed Mater Res A. 2003;  64 70-79
• 39 Alhadlaq A, Mao J J. Tissue-engineered neogenesis of human-shaped mandibular condyle from rat mesenchymal stem cells.  J Dent Res. 2003;  82 951-956
• 40 Patel P N, Smith C K, Patrick Jr C W. Rheological and recovery properties of poly(ethylene glycol) diacrylate hydrogels and human adipose tissue.  J Biomed Mater Res A. 2005;  73 313-319
• 41 Alcantar N A, Aydil E S, Israelachvili J N. Polyethylene glycol-coated biocompatible surfaces.  J Biomed Mater Res. 2000;  51 343-351
• 42 Martens P, Bryant S J, Anseth K S. Tailoring the degradation of hydrogels formed from multivinyl poly(ethylene glycol) and poly(vinyl alcohol) macromers for cartilage tissue engineering.  Biomacromolecules. 2003;  4 283-292
• 43 Coleman S R. Long-term survival of fat transplants: controlled demonstrations.  Aesthetic Plast Surg. 1995;  19 421-429
• 44 Patrick Jr C W, Friedrich J, Miller M J. Computer-assisted histometric analysis of tissue-engineered ovine bone.  Anal Quant Cytol Histol. 1998;  20 199-206
• 45 Patrick Jr C W. Adipose tissue engineering: the future of breast and soft tissue reconstruction following tumor resection.  Semin Surg Oncol. 2000;  3 302-311
• 46 Rahaman M N, Mao J J. Stem cell based composite tissue constructs for regenerative medicine.  Biotechnol Bioeng. 2005;  91 261-284