Cellular Derivatives and Efficacy in Wound and Scar Management

DOI: 10.4236/jcdsa.2013.31A007   PDF   HTML   XML   4,668 Downloads   6,955 Views   Citations


Biologicals have been used for decades in biopharmaceutical topical preparations. Because cellular therapies are routinely used in the clinic they have gained significant attention. Different derivatives are possible from different cell and tissue sources, making the selection of cell types and establishment of consistent cell banks crucial steps in the initial whole-cell bioprocessing. Various cell and tissue types have been used in treatment of skin wounds including autologous and allogenic skin cells, platelets, placenta and amniotic extracts from either human or animal sources. Experience with progenitor cells show that they may provide an interesting cell choice due to facility of out-scaling and known properties for wound healing without scar. Using defined animal cell lines to develop cell-free derivatives may provide initial starting material for pharmaceutical formulations that help in overall stability. Cell lines derived from ovine tissue (skin, muscle, connective tissue) can be developed in short periods of time and consistency of these cell lines was monitored by cellular life-span, protein concentrations, stability and activity. Each cell line had long culture periods up to 37 - 41 passages and protein measures for each cell line at passages 2 - 15 had only 1.4-fold maximal difference. Growth stimulation activity towards two target skin cell lines (GM01717 and CRL-1221; 40 year old human males) at concentrations ranging up to 6mg/ml showed 2-3-fold (single extracts) and 3-7-fold (co-cultured extracts) increase. Proteins from co-culture remained stable up to 1 year in pharmaceutical preparations shown by separation on SDS-PAGE gels. Pharmaceutical cell-free preparations were used for veterinary and human wounds and burns. Cell lines and cell-free extracts can show remarkable consistency and stability for preparation of biopharmaceutical creams, moreover when cells are co-cultured, and have positive effects for tissue repair.

Share and Cite:

A. Lapp, P. Furrer, A. Ramelet, C. Aubort, P. Aubort, P. Laurent and L. Applegate, "Cellular Derivatives and Efficacy in Wound and Scar Management," Journal of Cosmetics, Dermatological Sciences and Applications, Vol. 3 No. 1A, 2013, pp. 36-45. doi: 10.4236/jcdsa.2013.31A007.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] A. Limat, D. Mauri and T. Hunziker, “Successful Treatment of Chronic Leg Ulcers with Epidermal Equivalents Generated from Cultured Autologous Outer Root Sheath Cells,” Journal of Investigative Dermatology, Vol. 107, No. 1, 1996, pp. 128-135. doi:10.1111/1523-1747.ep12298415
[2] P. Bianco and P. G. Robey, “Stem Cells in Tissue Engineering,” Nature, Vol. 414, No. 6859, 2001, pp. 118-122. doi:10.1038/35102181
[3] K. M. Bullard, M. T. Longaker and H. P. Lorenz, “Fetal Wound Healing: Current Biology,” World Journal of Surgery, Vol. 27, No. 1, 2003, pp. 54-61. doi:10.1007/s00268-002-6737-2
[4] A. Kaviani, T. Perry, A. Dzakovic, R. W. Jennings, M. M. Ziegler and D. O. Fauza, “The Amniotic Fluid as a Source of Cells for Fetal Tissue Engineering,” Journal of Pediatric Surgery, Vol. 36, No. 11, 2001, pp. 1662-1665. doi:10.1053/jpsu.2001.27945
[5] A. Kaviani, T. Perry, C. M. Burnes, J.-T. Oh, M. M. Ziegler, S. J. Fishman and D. O. Fauza, “The Placenta as a Cell Source in Fetal Tissue Engineering,” Journal of Pediatric Surgery, Vol. 37, No. 7, 2002, pp. 995-999. doi:10.1053/jpsu.2002.33828
[6] C.-H. Wu, G.-Y. Chang, C.-T. Hsu and R.-S. Chen, “Wound Healing Effects of Porcine Placental Extracts on Rats with Thermal Injury,” British Journal of Dermatology, Vol. 148, No. 2, 2003, pp. 236-245. doi:10.1046/j.1365-2133.2003.05164.x
[7] S. R. Beanes, F. Y. Hu, C. Soo, C. M. Dang, M. Urata, K. Ting, J. B. Atkinson, P. Benhaim, M. H. Hedrick and H. P. Lorenz, “Confocal Microscopic Analysis of Scarless Repair in the Fetal Rat: Defining the Transition,” Plastic and Reconstructive Surgery, Vol. 109, No. 1, 2002, pp. 160-170. doi:10.1097/00006534-200201000-00026
[8] R. E. Fitzpatrick and E. F. Rostan, “Reversal of Photodamage with Topical Growth Factors: A Pilot Study,” Cosmetic and Laser Therapy, Vol. 5, No. 1, 2003, pp. 25-34 doi:10.1080/14764170310000817
[9] M. H. Gold, M. P. Goldman and J. Biron, “Efficacy of Novel Skin Cream Containing Mixture of Human Growth Factors and Cytokines for Skin Rejuvenation,” Journal of Drugs Dermatology, Vol. 6, No. 7, 2007, pp. 197-201.
[10] M. H. Gold and J. Biron, “A Novel Skin Cream Containing a Mixture of Human Growth Factors and Cytokines for the Treatment of Adverse Events Associated with Photodynamic Therapy,” Journal of Drugs Dermatology, Vol. 5, 2006, pp. 796-798.
[11] D. L. Cass, M. Meuli and N. S. Adzick, “Scar Wars: Implications of Fetal Wound Healing for the Pediatric Burn Patient,” Journal of Pediatric Surgery, Vol. 12, No. 7, 1997, pp. 484-489. doi:10.1007/BF01258707
[12] J. R. Armstrong and M. W. J. Ferguson, “Ontogeny of the Skin and the Transition from Scar Free to Scarring Phenotype during Wound Healing in the Pouch Young of the Marsupial Monodelphis domestica,” Developmental Biology, Vol. 169, No. 1, 1995, pp. 242-260. doi:10.1006/dbio.1995.1141
[13] C. Dang, K. Ting, C. Soo, M. T. Longaker and H. P. Lorenz, “Fetal Wound Healing Current Perspectives,” Clinics in Plastic Surgery, Vol. 30, No. 1, 2003, pp. 13-23. doi:10.1016/S0094-1298(02)00067-6
[14] J. Hohlfeld, A. de Buys Roessingh, N. Hirt-Burri, P. Chaubert, S. Gerber, C. Scaletta, P. Hohlfeld and L. A. Applegate, “Tissue Engineered Fetal Skin Constructs for Paediatric Burns,” Lancet, Vol. 366, No. 9488, 2005, pp. 840-842. doi:10.1016/S0140-6736(05)67107-3
[15] A. de Buys Roessingh, J. Hohlfeld, J. Scaletta, N. Hirt-Burri, S. Gerber, P. Hohlfeld, J.-O. Gebbers and L. A. Applegate, “Development, Characterization and Use of a Fetal Skin Cell Bank for Tissue Engineering in Wound Healing,” Cell Transplantation, Vol. 15, No. 8-9, 2006, pp. 823-834. doi:10.3727/000000006783981459
[16] A.-A. Ramelet, N. Hirt-Burri, W. Raffoul, Scaletta, D. P. Pioletti, E. Offord, R. Mansourian and L. A. Applegate, “Chronic Wound Healing by Fetal Cell Therapy may be Explained by Differential Gene Profiling Observed in Fetal Versus Old Skin Cells,” Experimental Gerontology, Vol. 44, No. 3, 2009, pp. 208-218.
[17] A. Quintin, N. Hirt-Burri, C. Scaletta, C. Schizas, D. Pioletti and L. A. Applegate, “Consistency and Safety of Fetal Cell Banks for Research and Clinical Use: Preliminary Analysis of Fetal Skin Banks,” Cell Transplantation, Vol. 16, No. 7, 2007, pp. 675-684.
[18] N. Hirt-Burri, C. Scaletta, S. Gerber, D. Pioletti and L. A. Applegate, “Wound Healing Gene-Family Expression Differences between Fetal and Foreskin Cells Used for Bioengineered Skin Substitutes,” Artificial Organs, Vol. 32, No. 7, 2008, pp. 509-518.
[19] A. R. Mire-Sluis, “Progress in the Use of Biological Assays during the Development of Biotechnology Products,” Pharmaceutical Research, Vol. 18, No. 9, 2010, pp. 1239-1246.
[20] M. P. Curran and G. L. Plosker, “Bilayered Bioengineered Skin Substitute (Apligraf): A Review of Its Use in the Treatment of Venous Leg Ulcers and Diabetic Foot Ulcers,” BioDrugs, Vol. 16, No. 6, 2002, pp. 439-455. doi:10.2165/00063030-200216060-00005
[21] Y. Kuroyanagi, N. Yamada, R. Yamashita and E. Uchinuma, “Tissue-Engineered Product: Allogeneic Cultured Dermal Substitute Composed of Spongy Collagen with Fibroblasts,” Artificial Organs, Vol. 25, No. 3, 2001, pp. 180-186. doi:10.1046/j.1525-1594.2001.025003180.x
[22] M. Fimiani, E. Pianigiani, F. C. Di Simplicio, P. Sbano, A. Cuccia, G. Pompella, G. De Aloe and F. Petaglia, “Other Uses of Homologous Skin Grafts and Skin Bank Bioproducts,” Clinics in Dermatology, Vol. 23, No. 4, 2005, pp. 396-402. doi:10.1016/j.clindermatol.2004.07.025
[23] K. W. Ng, H. L. Khor and D. W. Hutmacher, “In Vitro Characterization of Natural and Synthetic Dermal Matrices Cultured with Human Dermal Fibroblasts,” Biomaterials, Vol. 25, No. 14, 2004, pp. 2807-2818. doi:10.1016/j.biomaterials.2003.09.058
[24] V. Falanga, D. Margolis, O. Alvarez, M. Auletta, F. Maggiacomo, M. Altman, J. Jensen, M. Sabolinski, J. Hardin-Young and the Human Skin Equivalent Investigators Group, “Rapid Healing of Venous Ulcers and Lack of Clinical Rejection with an Allogeneic Cultured Human Skin Equivalent,” Archives of Dermatology, Vol. 134, No. 3, 1998, pp. 293-300. doi:10.1001/archderm.134.3.293
[25] P. Waymack, R. G. Duff, M. Sabolinski and The Apligraf Burn Study Group, “The Effect of a Tissue Engineered Bilayered Living Skin Analog, over Meshed Split-Thickness Autografts on the Healing of Excised Burn Wounds,” Burns, Vol. 26, No. 7, 2000, pp. 609-619. doi:10.1016/S0305-4179(00)00017-6
[26] B. Coulomb, C. Lebreton and L. Dubertret, “Influence of Human Dermal Fibroblasts on Epidermalization,” Journal of Investigative Dermatology, Vol. 92, No. 1, 1989, pp. 122-125.
[27] B. Coulomb, L. Friteau, J. Baruch, J. Guilbaud, B. Chretien-Marquet, J. Glicentstein, C. Lebreton-Decoster, E. Bell and L. Dubertret, “Advantage of the Presence of Living Dermal Fibroblasts within in Vitro Reconstructed Skin for Grafting in Humans,” Plastic and Reconstructive Surgery, Vol. 101, No. 7, 1998, pp. 1891-1903. doi:10.1097/00006534-199806000-00018
[28] H. A. Rackhorst, S. J. Posthumus-van Sluijs, M. W. Wendy, J. W. Van Neck, G. J. V. M. Van Osch, S. E. R. Hovius, A. Ghalbzouri and S. O. P. Hofer, “Fibroblasts Accelerate Culturing of Mucosal Substitutes,” Tissue Engineering, Vol. 12, No. 8, 2006, pp. 2321-2331. doi:10.1089/ten.2006.12.2321
[29] D. Nikolidakis, J. Van den Dolder, J. G. C. Wolke, P. J. W. Stoelinga and J. A. Jansen, “The Effect of Platelet-Rich Plasma on the Bone Healing around Calcium Phosphate-Coated and Non-Coated Oral Implants in Trabecular Bone,” Tissue Engineering, Vol. 12, No. 9, 2006, pp. 2555-2563. doi:10.1089/ten.2006.12.2555
[30] R. Nakoaka, S. X. Hsiong and D. J. Mooney, “Regulation of Chondrocyte Differentiaion Level via Co-Culture with Osteoblasts,” Tissue Engineering, Vol. 12, No. 9, 2006, pp. 2425-2433. doi:10.1089/ten.2006.12.2425

comments powered by Disqus

Copyright © 2020 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.