Article: Effect of amnion-derived cellular cytokine solution on healing of experimental partial-thickness burns

Background: Amnion-derived multipotent progenitor (AMP) cells, unlike most stem cells, have been demonstrated to be nontumorigenic and nonimmunogenic. Amnion-derived cellular cytokine solution (ACCS), a secreted product of AMP cells, is a cocktail of cytokines existing at physiological levels and has been used to accelerate epithelialization of experimental partial-thickness burns.

Methods: Using modifications of Zawacki's guinea pig partial-thickness scald burn model, a total of 65 animals were treated with ACCS, ACCS + AMP cells, unconditioned medium (UCM) + AMP cells, or either UCM alone or saline as controls. Dosage times ranged from every other day to once a week. Percent epithelialization was serially determined from acetate wound tracings. Histology was performed on wound biopsies.

Results: ACCS, UCM + AMP cells, and ACCS + AMP cells improved epithelialization compared with the two control groups (P < 0.05). When ACCS was delivered more frequently, statistically significant more rapid epithelialization occurred (P < 0.05). By day 7, all groups treated with ACCS had reached at least 90% epithelialization, whereas control groups were only 20-40% epithelialized (P < 0.05). Histology showed excellent regeneration of the epidermis with rete ridge formation. Hair growth occurred in ACCS-treated animals but not in the control group.

Conclusions: Amnion-derived cellular cytokine solution accelerates the healing of experimental partial-thickness burns. Based on these findings, a multicenter clinical trial is underway.

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References

1.

Uberti M, Ko F, Pierpont Y, Johnson E, Wright T, Smith C . The use of amnion-derived cellular cytokine solution (ACCS) in accelerating closure of interstices in explanted meshed human skin grafts. Eplasty. 2009; 9:e12. PMC: 2664608. View

2.

Saranto J, Rubayi S, Zawacki B . Blisters, cooling, antithromboxanes, and healing in experimental zone-of-stasis burns. J Trauma. 1983; 23(10):927-33. DOI: 10.1097/00005373-198310000-00015. View

3.

Xing L, Franz M, Marcelo C, Smith C, Marshall V, Robson M . Amnion-derived multipotent progenitor cells increase gain of incisional breaking strength and decrease incidence and severity of acute wound failure. J Burns Wounds. 2007; 7:e5. PMC: 2064968. View

4.

Dvonch V, Murphey R, Matsuoka J, Grotendorst G . Changes in growth factor levels in human wound fluid. Surgery. 1992; 112(1):18-23. View

5.

Franz M, Payne W, Xing L, Naidu D, Salas R, Marshall V . The use of amnion-derived cellular cytokine solution to improve healing in acute and chronic wound models. Eplasty. 2008; 8:e21. PMC: 2323202. View

6.

Han S, Yoon T, Lee D, Lee M, Kim W . Potential of human bone marrow stromal cells to accelerate wound healing in vitro. Ann Plast Surg. 2005; 55(4):414-9. DOI: 10.1097/01.sap.0000178809.01289.10. View

7.

Zawacki B . Reversal of capillary stasis and prevention of necrosis in burns. Ann Surg. 1974; 180(1):98-102. PMC: 1343615. DOI: 10.1097/00000658-197407000-00015. View

8.

DELBECCARO E, ROBSON M, Heggers J, Swaminathan R . The use of specific thromboxane inhibitors to preserve the dermal microcirculation after burning. Surgery. 1980; 87(2):137-41. View

9.

ROBSON M, DELBECCARO E, Heggers J, Loy G . Increasing dermal perfusion after burning by decreasing thromboxane production. J Trauma. 1980; 20(9):722-5. DOI: 10.1097/00005373-198009000-00002. View

10.

Hammond S, Tsonis C, Sellins K, Rushlow K, Scharton-Kersten T, Colditz I . Transcutaneous immunization of domestic animals: opportunities and challenges. Adv Drug Deliv Rev. 2000; 43(1):45-55. DOI: 10.1016/s0169-409x(00)00076-4. View

11.

Banas R, Trumpower C, Bentlejewski C, Marshall V, Sing G, Zeevi A . Immunogenicity and immunomodulatory effects of amnion-derived multipotent progenitor cells. Hum Immunol. 2008; 69(6):321-8. DOI: 10.1016/j.humimm.2008.04.007. View

12.

Steed D, Trumpower C, Duffy D, Smith C, Marshall V, Rupp R . Amnion-derived cellular cytokine solution: a physiological combination of cytokines for wound healing. Eplasty. 2008; 8:e18. PMC: 2311453. View

Effect of Amnion-derived Cellular Cytokine Solution on Healing of Experimental Partial-thickness Burns