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Lentiviral gene transfer of SDF-1alpha to wounds improves diabetic wound healing.
J Surg Res 2007; 143(1):35-42JS

Abstract

BACKGROUND

Chronic wounds continue to be a major clinical problem and novel therapeutic approaches are needed. We have previously demonstrated that treatment of diabetic mouse wounds with local application of stromal progenitor cells results in improved healing and increased production of stromal-derived growth factor-1alpha (SDF-1alpha). We hypothesized that lentiviral-mediated increased production of SDF-1alpha in the wound environment could also improve diabetic wound healing.

MATERIALS AND METHODS

Full-thickness excisional wounds were created in Db-/Db- mice and immediately treated with 10(6), 10(8), or 10(9) plaque-forming units of a lentiviral construct containing GFP-SDF-1alpha or GFP alone. At 7 and 14 days post wounding, wounds were harvested for histological and molecular analysis.

RESULTS

At 7 days, Db-/Db- wounds treated with lenti GFP-SDF-1alpha exhibited a decrease in wound surface area for all doses tested. Morphologically, SDF-treated wounds were more cellular with increased granulation tissue volume compared to controls (P < 0.05). GFP expression was maintained in treated tissue at 7 days post wounding, but little expression was observed at 14 days. While we did not observe a difference in the gross wound surface area at 14 days, histological analysis revealed that SDF-treated wounds were fully epithelialized (n = 6) compared to only one of six controls.

CONCLUSIONS

Lentiviral-mediated overproduction of SDF-1alpha is sufficient to correct the pathophysiologic abnormalities in diabetic wound healing resulting in complete epithelialization at 2 weeks. SDF-1alpha-mediated improvement in diabetic wound healing has significant implications for the development of novel therapeutic strategies to facilitate wound closure which target progenitor cell mobilization and recruitment.

Authors+Show Affiliations

The Center for Fetal Research at The Children's Hospital of Philadelphia, The University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17950070

Citation

Badillo, Andrea T., et al. "Lentiviral Gene Transfer of SDF-1alpha to Wounds Improves Diabetic Wound Healing." The Journal of Surgical Research, vol. 143, no. 1, 2007, pp. 35-42.
Badillo AT, Chung S, Zhang L, et al. Lentiviral gene transfer of SDF-1alpha to wounds improves diabetic wound healing. J Surg Res. 2007;143(1):35-42.
Badillo, A. T., Chung, S., Zhang, L., Zoltick, P., & Liechty, K. W. (2007). Lentiviral gene transfer of SDF-1alpha to wounds improves diabetic wound healing. The Journal of Surgical Research, 143(1), pp. 35-42.
Badillo AT, et al. Lentiviral Gene Transfer of SDF-1alpha to Wounds Improves Diabetic Wound Healing. J Surg Res. 2007;143(1):35-42. PubMed PMID: 17950070.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lentiviral gene transfer of SDF-1alpha to wounds improves diabetic wound healing. AU - Badillo,Andrea T, AU - Chung,Sophie, AU - Zhang,Liping, AU - Zoltick,Philip, AU - Liechty,Kenneth W, PY - 2007/01/03/received PY - 2007/03/01/revised PY - 2007/03/04/accepted PY - 2007/10/24/pubmed PY - 2007/12/14/medline PY - 2007/10/24/entrez SP - 35 EP - 42 JF - The Journal of surgical research JO - J. Surg. Res. VL - 143 IS - 1 N2 - BACKGROUND: Chronic wounds continue to be a major clinical problem and novel therapeutic approaches are needed. We have previously demonstrated that treatment of diabetic mouse wounds with local application of stromal progenitor cells results in improved healing and increased production of stromal-derived growth factor-1alpha (SDF-1alpha). We hypothesized that lentiviral-mediated increased production of SDF-1alpha in the wound environment could also improve diabetic wound healing. MATERIALS AND METHODS: Full-thickness excisional wounds were created in Db-/Db- mice and immediately treated with 10(6), 10(8), or 10(9) plaque-forming units of a lentiviral construct containing GFP-SDF-1alpha or GFP alone. At 7 and 14 days post wounding, wounds were harvested for histological and molecular analysis. RESULTS: At 7 days, Db-/Db- wounds treated with lenti GFP-SDF-1alpha exhibited a decrease in wound surface area for all doses tested. Morphologically, SDF-treated wounds were more cellular with increased granulation tissue volume compared to controls (P < 0.05). GFP expression was maintained in treated tissue at 7 days post wounding, but little expression was observed at 14 days. While we did not observe a difference in the gross wound surface area at 14 days, histological analysis revealed that SDF-treated wounds were fully epithelialized (n = 6) compared to only one of six controls. CONCLUSIONS: Lentiviral-mediated overproduction of SDF-1alpha is sufficient to correct the pathophysiologic abnormalities in diabetic wound healing resulting in complete epithelialization at 2 weeks. SDF-1alpha-mediated improvement in diabetic wound healing has significant implications for the development of novel therapeutic strategies to facilitate wound closure which target progenitor cell mobilization and recruitment. SN - 0022-4804 UR - https://www.unboundmedicine.com/medline/citation/17950070/Lentiviral_gene_transfer_of_SDF_1alpha_to_wounds_improves_diabetic_wound_healing_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-4804(07)00186-2 DB - PRIME DP - Unbound Medicine ER -