J Korean Med Sci.  2014 Mar;29(3):311-319. 10.3346/jkms.2014.29.3.311.

Cell Therapy for Wound Healing

• You HJ
• Han SK

• KMID: 1734915
• DOI: http://doi.org/10.3346/jkms.2014.29.3.311

Abstract

In covering wounds, efforts should include utilization of the safest and least invasive methods with goals of achieving optimal functional and cosmetic outcome. The recent development of advanced wound healing technology has triggered the use of cells to improve wound healing conditions. The purpose of this review is to provide information on clinically available cell-based treatment options for healing of acute and chronic wounds. Compared with a variety of conventional methods, such as skin grafts and local flaps, the cell therapy technique is simple, less time-consuming, and reduces the surgical burden for patients in the repair of acute wounds. Cell therapy has also been developed for chronic wound healing. By transplanting cells with an excellent wound healing capacity profile to chronic wounds, in which wound healing cannot be achieved successfully, attempts are made to convert the wound bed into the environment where maximum wound healing can be achieved. Fibroblasts, keratinocytes, adipose-derived stromal vascular fraction cells, bone marrow stem cells, and platelets have been used for wound healing in clinical practice. Some formulations are commercially available. To establish the cell therapy as a standard treatment, however, further research is needed.

Keyword

Cell-and Tissue-based Therapy; Wounds and Injuries; Tissue Engineering

MeSH Terms

Blood Platelets/metabolism
Cell- and Tissue-Based Therapy
Diabetes Mellitus, Type 2/complications/pathology
Fibroblasts/cytology/transplantation
Humans
Keratinocytes/cytology/transplantation
Stromal Cells/cytology/transplantation
Tissue Engineering
Ulcer/etiology/therapy
*Wound Healing

Figure

• 

  Fig. 1 Treatment of a diabetic foot ulcer using an allogeneic keratinocyte sheet. A woman (aged 63 yr) with a chronic non-healing diabetic ulcer over 10 weeks old on the medial side of the right fifth toe. After debridement, freshly bleeding wound bed was prepared. (A) View of the cultured allogeneic keratinocyte sheet. (B) Preoperative view. (C-E) Wound appearance was taken every week. Re-epithelization occurred progressively from the periphery to the center of the wound. The wound was completely healed after 3 weeks.

• 

  Fig. 2 Cheek defect created by removal of a basal cell carcinoma was reconstructed by autologous fibroblasts seeded on a hyaluronic acid sheet. The entire wound re-epithelialized 21 days after grafting. (A and B) Fibroblast pellet and non-woven hyaluronic acid sheet. (C) After wide excision of the tumor. (D) Immediately after the graft of the tissue-engineered dermis. (E) One-year after the graft. The result demonstrates excellent color match with minimal scar contracture.

• 

  Fig. 3 A woman (aged 50 yr) with 6 week old chronic non-healing diabetic ulcers on the left second and third toe tips. The second toe with the larger wound was treated with the fibroblast allograft, and the third toe with the smaller wound was conservatively treated. (A) Preoperative view. (B) Immediate after treatments. (C) Two weeks after treatments. (D) Twenty days after treatments, the second toe wound completely epithelized, but the third toe wound (control) had a raw surface. (E) Three months after treatments, the second toe was good with a healthy texture, but the third toe had not yet completely epithelized.

• 

  Fig. 4 Reconstruction using stromal vascular fraction (SVF) cells. (A) A squamous cell carcinoma on the hand. (B) After wide excision of the tumor, flap surgery was required since the first metacarpal bone and tendons were exposed. However, a procedure which needs a general anesthesia or a long operation time could not be performed due to the poor general health condition of the patient. (C and D) To prepare the wound bed to be allowed for a skin graft, stromal vascular cells were isolated and grafted on the wound bed. (E) Three weeks after the graft, a healthy granulation tissue was formed. (F) The wound was finally closed by a split-thickness skin graft under local anesthesia.

• 

  Fig. 5 Results of a stromal vascular fraction (SVF) cell graft applied to a thumb. (A) A bone and pulp defect on the thumb caused by trauma. Black and yellow arrows indicate the cortex and medulla of the distal phalanx, respectively. (B) SVF cells suspended in fibrin glue were transplanted one day after trauma. (C-F) Two-weeks, 4-weeks, 3-months, and 1-yr after the graft. The wound was completely closed 4 weeks after the graft.

• 

  Fig. 6 A 73-yr-old man with diabetes mellitus had a non-healing ulcer over 8 weeks old on the anterior tibial area of the lower leg. (A) A large wound on the lower leg with exposed tibial bone (an arrow). (B) Drilling in the bone to take out bone marrow stromal stem cells (BSCs). (C-E) Two, 3, and 4 weeks after drilling. Granulation tissue was formed from the drilling sites. (F) The wound was closed by a skin graft.

• 

  Fig. 7 A 67-yr-old man with diabetes mellitus had a non-healing ulcer on the lateral border of his right foot at the metatarsophalangeal joint level. Before participating in the study, the patient had been treated for 12 weeks. (A) Preoperative view. (B) After surgical debridement, the metatarsal and proximal phalangeal bones were exposed. (C) Three days after the first application of blood bank platelet concentrate (BBPC) (immediate before the second application of the BBPC). (D) Three weeks after the first application of BBPC. (E) Five weeks after the first application of BBPC. (F) Seven weeks after treatment, the wound was completely epithelialized. Two applications were performed for this patient.

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