A Prospective Multicenter Study of the Efficacy and Tolerability of Cryopreserved Allogenic Human Keratinocytes to Treat Venous Leg Ulcers

Abstract

Allogeneic human keratinocyte cultures have been used to treat burn wounds, donor sites, and chronic skin ulcers with some success. Cryopreservation of these cultures allows for the production of large standardized batches that are readily available for use. The aim of the study presented in this report was to study effects of cryopreserved cultured allogenic human keratinocytes (CryoCeal) on chronic lower extremity wounds. Parameters were measured to study efficacy, tolerability, pain associated with chronic wounds, and quality of life of patients. Twenty-seven patients with hard-to-heal venous leg ulcers received a maximum of 9 applications of CryoCeal in a prospective, uncontrolled multicenter study lasting 48 weeks. Eleven out of 27 patients (41%; 95% CI: 22%-61%) had complete wound closure within 24 weeks (1 week). The time required for complete wound closure in these 11 patients ranged from 4.1 to 24.9 weeks. Only 1 patient had recurrence of the ulcer at 48 weeks. Local (wound) pain scores decreased from a mean of 2.5 at baseline to 0.9 at week 24. Fifty percent of the patients attained a pain score of 0 after 12 weeks and remained stable at this score until the end of the study. Overall, the patient quality of life was better at week 24, compared to baseline values. The treatment was well tolerated, and wound infection was the most frequently occurring adverse event.

Use of amniotic membrane transplantation in the treatment of venous leg ulcers

“…The fact that the healing benefit still persists after 4 weeks suggests the initiation of a persistent wound‐healing process induced by an AM graft. The stimulatory effect on epithelialization from the ulcer bed and /or the wound edge is considered to be mediated by growth factors and progenitor cells released by AM 4,19 . The lack of long‐term persistence of AM in chronic leg ulcers might be mostly in relation to the highly inflammatory environment of the leg ulcer, although immune‐mediated rejection could also be contributory.…”

“…The stimulatory effect on epithelialization from the ulcer bed and /or the wound edge is considered to be mediated by growth factors and progenitor cells released by AM. 4,19 The lack of long-term persistence of AM in chronic leg ulcers might be mostly in relation to the highly inflammatory environment of the leg ulcer, although immune-mediated rejection could also be contributory. Despite a transient class-I HLA antibody response detected in one patient and strong class I expression observed in the amniotic epithelium, mesenchymal cells, and fibroblasts in cryopreserved AM, 20 AM seems to be an immune-privileged tissue and to contain immunoregulatory factors, including HLA-G and Fas ligands which may account for the fact that immunological rejection after AM transplantation has not yet been observed in an immune-privileged site: the eye 6,20 vs. the skin here.…”

Feeder layer- and animal product-free culture of neonatal foreskin keratinocytes: improved performance, usability, quality and safety

“…O’Connor et al (1981) reported the use of autologous keratinocyte cultures for the treatment of burns, and over time an increasing number of culture and delivery systems of epithelial grafts were developed, mainly in the burn care field (Madden et al 1986; Herzog et al 1988; Burt et al 1989; Compton et al 1990; De Luca et al 1989; Bolivar-Flores et al 1990; Fratianne et al 1993; Phillips et al 1993; Rue et al 1993; Teepe et al 1993a; Brychta et al 1995, Rivas-Torres et al 1996; Carsin et al 2000; Hiroko et al 2001; Koller et al 2002; Chester et al 2004), but also in dermatology (Roseeuw et al 1989; Teepe et al 1990; De Luca et al 1992; Marcusson et al 1992; Teepe et al 1993b; Lindgren et al 1998; Beele et al 2005), otology (Somers et al 1997a; Somers et al 1997b) and stomatology (Tsai et al 1997). Unfortunately, due to wide patient-to-patient variation and the lack of controlled clinical research, it is currently difficult to tell whether there is a place for cultured epithelial grafts in the treatment of major burns (Wood et al 2006).…”

Mathematical model for wound healing following autologous keratinocyte transplantation

“…In other studies, wound healing varied between 26 and 39Á9 days after transplantation of allogenic cryopreserved cultured keratinocytes. The size of the ulcer was mainly reduced rapidly within the first to fourth week (10)(11)(12)(13)(14). The authors believe that this is not only because of the release of different cytokines and growth factors by the transplanted keratinocytes but probably also because of deposition of extracellular matrix and basement membrane components.…”