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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 33  |  Issue : 2  |  Page : 694-698

Potential of stem cells for skin regeneration following burn


1 Department of Plastic and Reconstructive Surgery, Faculty of Medicine, Menoufia University, Shebeen El-Kom, Egypt
2 Department of Clinical Pathology, Faculty of Medicine, Menoufia University, Shebeen El-Kom, Egypt
3 Plastic and Reconstructive Surgery Department, El-Mehalla El-Kobra General Hospital, Gharbia, Egypt

Date of Submission05-Feb-2019
Date of Decision05-Mar-2019
Date of Acceptance10-Mar-2019
Date of Web Publication27-Jun-2020

Correspondence Address:
Ahmed I. F. Ibrahim
Mehalla El-Kobra, Gharbia 32717
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_48_19

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  Abstract 


Objective
To evaluate the possible additive effects of the use of stem cells for skin regeneration following superficial burn.
Background
Stem cell therapy has offered a great method in the management of burns. There are different sources of stem cell, such as adipose tissue-derived stem cells (ADSCS), bone marrow-derived stem cells, umbilical cord-derived stem cells, or amniotic fluid stem cells. We tried to prove the potential of ADSCS in the management of superficial burn.
Patients and methods
This clinical trial was performed at the Department of Plastic and Reconstructive Surgery, Menoufia University Hospital, from January 2014 to January 2016. It was done on 30 patients with superficial burn. The ages of the patients ranged from 20 to 60 years. Patients were of both sexes, who were divided into two groups: group A was scheduled for application of ADSCS in burnt area after its isolation by liposuction, and group B was scheduled for application of silver sulfadiazine.
Results
Postoperative follow-up assessment took place on the third, fifth, seventh, 14th, and 21st day. The supervisors and researchers assessed results based on clinical observation and analysis of the preoperative and postoperative photographs, with significant superiority of using ADSCSs with respect to rapid healing, pain tolerance, and patient's satisfaction.
Conclusion
Adipose tissue-derived mesenchymal stem cell dressing application can be an option and may become an ideal therapy in the treatment of superficial burn. Its use would shorten the period of healing and provide a cheap alternative to other techniques.

Keywords: adipose tissue, burn, liposuction, skin, stem cell


How to cite this article:
Keshk TF, El-Sakka DM, Nassar AT, Omar TA, Ibrahim AI. Potential of stem cells for skin regeneration following burn. Menoufia Med J 2020;33:694-8

How to cite this URL:
Keshk TF, El-Sakka DM, Nassar AT, Omar TA, Ibrahim AI. Potential of stem cells for skin regeneration following burn. Menoufia Med J [serial online] 2020 [cited 2020 Oct 22];33:694-8. Available from: http://www.mmj.eg.net/text.asp?2020/33/2/694/287806




  Introduction Top


Burn injury is considered to be an important cause of morbidity and mortality all over the world. It leads to a loss of integrity of the skin that protects us from water loss, temperature change, trauma, and infection. Stem cell therapy has emerged as a promising treatment strategy, not only for burn healing but also to treat systemic effects of burn trauma, inflammation, and immunosuppression[1],[2]. When classified by origin, there are two types of stem cells: embryonic and nonembryonic stem cells. The latter is also referred to as adult or somatic stem cells[3],[4]. The main sources of adult stem cells are as follows: (a) bone marrow-derived stem cells: bone marrow has been the primary source of mesenchymal stem cells; however, bone marrow collection is invasive and Mesenchymal Stem Cells (MSC) isolation is inefficient[5],[6]; (b) adipose tissue-derived stem cells (ADSCs): ADSCs are multipotent somatic stem cells that can differentiate into several lineages, including adipose cells, chondrocytes, osteoblasts, and neuronal cells[7]. The existence of stem cells within adipose tissue was reported for the first time in 2001[8] ADSCs differ depending on their anatomical sites and depending on their type (white or brown)[9]. Current research suggests that they may actually be pluripotent and form cell types of all three germ layers[10]. ADSCs represent a promising source of adult mesenchymal stem cells, mainly because isolation is less invasive and more efficient[11],[12]. Aspirated fat is obtained in many plastic surgery procedures, for example, liposuction, and precursor cells can be purified to obtain the ADSC-rich stromal vascular fraction (SVF)[13]. The SVF is a heterogeneous mixture containing endothelial cells, preadipocytes, fibroblasts, vascular cells, macrophages, and numerous mesenchymal stem cells[11]; and (c) umbilical cord (blood)-derived stem cells[5]. ADSCs is isolated by liposuction, which are easily obtainable in adequate quantities as compared with bone marrow, umbilical cord, or amniotic fluid sources. Mesenchymal stem cells are extracted from adipose tissue, representing a promising, easy, abundant, and cost-effective source[14]. These stem cells have many advantages such as its plasticity, which refers to the ability of stem cells isolated from a single type of tissue to transform into cells of similar and different embryonic germ layer. Another special characteristic of stem cells is pluripotency, where the cells are undifferentiated and have the capability to generate other kinds of cells, which also include new stem cells identical to the mother cell[15]. ADSCs represent a promising source of mesenchymal stem cells, mainly because isolation is less invasive and more efficient[11]. It is worth mentioning, besides being one of the richest sources of adult stem cells in the human body, adipose tissue is also an endocrine organ that secretes numerous hormones, growth factors, and cytokines that support wound healing, such as epidermal growth factor, fibroblast growth factor, keratinocyte growth factor, transforming growth factor-β, and vascular endothelial growth factor[11],[16].

The aim of this study is to evaluate a possible additive effect of the application of stem cells for skin regeneration following superficial burn.


  Patients and Methods Top


This prospective study was conducted at the Department of Plastic and Reconstructive Surgery, Menoufia University Hospital, from January 2014 to January 2016. It was approved by the ethical committee on July 2016. It included 30 (18 females and 12 males) patients with superficial burn. The mean age was 31.1 years old for the study group and 32.4 years old for the control group. All the patients signed an informed consent for photography before and after surgical procedures, including publication for research issues. The patients were of both sexes divided into two groups:

  1. Group I was the study group, which included 15 patients. Adipose tissue-derived mesenchymal stem cell dressing was used for the treatment of the superficial burns
  2. Group II was the control group, which included 15 patients. Silver sulfadiazine application was used for the treatment of the superficial burns.


All patients were seen within 24 h of occurrence of burn. They received first aid measure for burn. The patients were selected as an example of superficial burns to evaluate the role of stem cells as treatment of such cases. Fat was harvested by liposuction from the patient's abdomen (the extraction was performed using an aspiration nozzle with a diameter of 3 mm and length of 15 cm. A negative pressure vacuum was created in the syringe manually and gradually to avoid high pressure that could harm the adipocytes).

Once human fat is obtained, either through liposuction, it was placed in sterile, ice-filled plastic bags and sent to the laboratory.

The extracted tissue was aseptically homogenized and then taken to a biological exposure chamber, where the tissue is repeatedly washed with PBS until all visible blood and excessive fluids are eliminated, to leave fat as clean as possible.

The washed fat was placed in a magnetic stirrer for 1 h at 37°C. Afterward, the fat undergoes enzymatic digestion, with the addition of a solution prepared with Dulbecco's modified Eagle medium, type a collagenase, penicillin, and streptomycin. After 1 h, the digestion is interrupted with the addition of bovine fetal serum. The resultant material was centrifuged, and the floating fraction was discarded. The portion sitting at the bottom of the centrifuged tube (called pellet), which is the one containing the so-called SVF, was transferred to bottles filled with Dulbecco's modified Eagle medium, bovine fetal serum, penicillin, and streptomycin. The cells were taken to an incubator at 37°C, under 5% CO2, and were washed with PBS, resulting in their adhesion to the bottom of the plastic bottles. After washing, stem cell suspension was ready to be applied over the burned area. The burned area was washed by ordinary saline, any necrotic tissues are removed, and the amount of suspension is suitable to cover the burned area and is measured as every 1-cm2 burned area covered with 1 cm3 fat by liposuction transformed to SVF that was suspended into 1 cm3 of PBS. Then, the burned area was covered with sterilized dressing and bandage till the next session on the third, fifth, seventh, 14th, and 21st days. The steps were repeated as mentioned till full healing. Postoperative follow-up assessment took place according to the previous schedule. The supervisors and researchers assessed results based on clinical observation and analysis of the preoperative and postoperative photographs, using a Likert scale of five values: no result obtained (1), poor improvement (2), fair visible result (3), good result (4), and excellent result (5).

The follow-up parameters are as follows: (a) total area epithelized at the end of intervention is measured in cm2, (b) healing rate of the wound, (c) color of the wound, (d) size of the wound, and (e) duration of complete wound healing.

Statistical analysis

All data were collected, tabulated, and statistically analyzed. The descriptive measures of central tendency (mean and median) and measures of dispersion (range, SD, minimum and maximum), besides frequency and the percentage, were calculated by statistical package for the social sciences 20 (SPSS, SPSS Inc., Chicago, Illinois, USA).


  Results Top


The work was done on 30 patients divided into two groups; both groups had superficial degree of burn:

  1. Group A (study group): it included 15 patients; in this group, we used adipose-derived mesenchymal stem cell dressing for treatment of burn
  2. Group B (control group): it included 15 patients, where only silver sulfadiazine was used for treatment of burn.


The site of the burn varied widely; it included face, neck, upper limbs, or lower limbs.

[Figure 1] and [Figure 2] demonstrate the variance between the study and the control groups regarding the different sites of burn.
Figure 1: Group 1 (study group) burn site.

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Figure 2: Group 2 (control group) burn site.

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Healing was assessed at regular intervals on the third, fifth, seventh, 14th and 21th day of occurrence of burn till complete healing.

The assessment was based on epithelialization and area of coverage of burnt site as shown in [Table 1].
Table 1: Comparing the full healing time between the two groups

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In group A (study group), eight (53%) cases achieved complete healing on the seventh day, whereas five (33%) cases achieved complete healing on the 14th day.

In group B (control group), healing rate was poor, as only two (13%) cases achieved complete healing on the seventh day, whereas 11 (73%) cases achieved complete healing on the 14th day, and two (13%) cases healed later on 21th day.

There was a significant difference between the healing progress in both groups, with better results in the study group patients (P = 0.0002; [Figure 3] and [Figure 4]).
Figure 3: Superficial burn of left hand before and 7 days after application of stem cells.

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Figure 4: Superficial burn of left hand before and 14 days after application of silver sulfadiazine.

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There were marked improvements of pain sensation at burnt wound site in the study group (measured by visual analogue scale), with P value of 0.004, which is statistically significant compared with group II, with P value 0.106, which is statistically insignificant.

Satisfaction of patients was evaluated by subjective questionnaire of patients. Overall, 100% of patients in the study group were satisfied in comparison with only 40% of group B.


  Discussion Top


Burn injuries are one of the most common causes of trauma, which have significant effects on long-term personal and health care cost. The goal of burn wound healing is to fully repair and restore skin's structure and function.

One of the ways this can be achieved is through regenerative capability of stem cells.

The study tried to highlight recent developments in treatment of burn wounds employing stem cells. It was conducted on 30 patients, including 15 patients who were subjected to autologous stem cell dressing application, whereas the other 15 patients were subjected to silver sulfadiazine dressing as a control group. Burned sites are face, hand, foot, limbs, and trunk.

The conclusion from this study is that the use of adipose-derived stem cells dressing application in treating burned area was an effective treatment option, as we found complete healing in all our cases earlier, with less pain sensation and more satisfaction, compared with silver sulfadiazine dressing.

ADSC suspension was used to cover the burned area by simple application and not by injection, because it was simple and less painful, and there is no difference in the result between application by simple coverage and injection.

Sandel[17] argued that embryonic stem cell harvesting would be done by killing embryos, which would be unethical, whereas others argued that even if embryos are used for stem cell research, it is not wrong. However, the path that this may lead to would be wrong, owing to embryo 'production' for research purposes. In comparison, Shumakov et al.[18] used mesenchymal bone marrow-derived stem cells in burn wound healing and compared them with embryonic fibroblasts. Afemale patient with extensive skin burns (IIIB 30% of body surface area) had the stem cells applied onto the burn surface. The study agreed with Shumakov et al.[18] who applied stem cells onto the burned surface. The application of stem cells resulted in faster wound healing, but bone marrow is still a difficult and hazardous source. Natesan et al.[19] used debrided skin from severe burns as a source of stem cells for wound healing and regeneration. Hence, the adipose tissue that is discarded from burn wound debridement may now be of use for better wound healing.

Along the same line, van der Veen et al.[20] isolated mesenchymal stem cells from excised burn wound eschar.

This is in agreement with Chan et al.[21] who isolated autologous stem cells from the adipose layer of surgically debrided burned skin. The results indicate that stem cells isolated from debrided skin can be used as a single autologous cell source to develop a vascularized skin construct without culture expansion or addition of growth factors. The study provides an alternative approach for cutaneous coverage after extensive burn injuries but in a simple, safe, and more effective way. The harvested adipose tissue by liposuction was spread on burned areas by simple application, whereas Klinger et al.[22] used fat injections in burn wounds as a trial to improve burn wound healing in humans. Results showed scar improvement and enhancement of tissue regeneration, but their study was limited to a small population in comparison with our study.

Regarding the costs, ATSC by liposuction under local anesthesia offered a simple and cheap source compared with Abdallah Hajj Hussein et al.[23] who studied the effect of Botox injections on burn wound healing and found that Botox increased fibroblasts transforming growth factor-β and tumor necrosis factor-α levels and decreased inflammation, thus improving burn wound healing.

Lataillade et al.[24] reported two cases where stem cells were used to aid in burn wound healing. The application of the mesenchymal stem cells decreased the levels of inflammation and promoted better healing.


  Conclusion Top


Adipose tissue-derived mesenchymal stem cell application can be an option and may become an ideal therapy in the treatment of superficial burned areas. ATSC application would shorten the period of healing. It is safe, based on the absence of complications in our study, with no adverse effects, less pain, and more patient satisfaction.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
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