International Journal of Dermatology, Venereology and Leprosy Sciences.

2020; 3(2): 21-26

E-ISSN: 2664-942X
P-ISSN: 2664-9411
www.dermatologypaper.com New approach to deep diabetic foot ulcer (DFU)
Derma 2020; 3(2): 21-26
Received: 28-04-2020 treatment-potential of secretome from Wharton’s jelly
Accepted: 16-06-2020
mesenchymal stem cell therapy
Sukmawati Tansil Tan
Departement of Dermato-
Venerology, Tarumanagara Sukmawati Tansil Tan, Yohanes Firmansyah and Jessica Elizabeth
University, Jakarta, Indonesia
DOI: https://doi.org/10.33545/26649411.2020.v3.i2a.41
Yohanes Firmansyah
Departement of Dermato-
Venerology, Tarumanagara Abstract
University, Jakarta, Indonesia Diabetic foot ulcer is one of the complications of chronic diabetes in the form of lesions in deep tissue
and associated neurological disorders and peripheral vascular disease in the lower limbs. DFU has a
Jessica Elizabeth significant impact on the health and quality of life of patients and their families. The effect that is often
Departement of Dermato- felt is ranging from pain, loss of function and mobility, depression, difficulty and anxiety, shame,
Venerology, Tarumanagara social isolation, the financial burden of extended hospital stays and chronic morbidity, or even
University, Jakarta, Indonesia amputation to death. This case report reports the case of a 64-year-old man with DFU grade 3 and has
been advised to undergo a finger amputation surgery by a surgeon to prevent infection, and the finger is
predicted to be untenable. After intervention with a single dose, intracutaneous injection of Secretome
from-Placental Wharton Jelly Stem Cell (SC-PWJSC), regular insulin, and control Sugar Blood
Glucose. There is a very significant wound repair. Patients reported being satisfied with this treatment.

Keywords: Diabetic foot ulcer, diabetes mellitus, cutaneous injection, SC-PWJSC

Introduction
1. Background
Diabetic foot ulcer is one of the complications of chronic diabetes in the form of lesions in
deep tissue and associated neurological disorders and peripheral vascular disease in the lower
limbs [1]. The incidence of diabetic foot ulcers has increased due to the prevalence of diabetes
mellitus worldwide and the better life expectancy of diabetic patients. Literature searches
show that every 30 seconds, an amputation occurs in the lower extremities due to diabetes [2],
and caused a significant health cost burden of $ 8659 per patient [3]. Total medical costs for
treating diabetic foot disease in the United States range from $ 9 to $ 13 billion and are
additional costs associated with diabetes [4]. The International Diabetes Foundation has
appealed to the public to increase awareness of diabetic foot disease due to a substantial
social, medical, and economic burden [5]. Of all amputations in diabetic patients, 85% are
preceded by foot ulceration which then worsens into severe gangrene or infection which is
difficult to resolve [6].
The prevalence of diabetic foot ulcers globally reaches 6.3% (95% CI: 5.4-7.3%), which is
higher in men (4.5%, 95% CI: 3.7-5.2%) compared to women (3.5%, 95% CI: 2.8-4.2%),
and higher in patients with type 2 diabetes (6.4%, 95% CI: 4.6-8.1%) compared to people
with type 1 diabetes (5.5%, 95% CI: 3.2-7.7%). North America has the highest prevalence
(13.0%, 95% CI: 10.0-15.9%), Oceania has the lowest (3.0%, 95% CI: 0.9-5.0%), and
prevalence in Asia, Europe, and Africa respectively 5.5% (95% CI: 4.6–6.4%), 5.1% (95%
CI: 4.1–6.0%), and 7.2% (95% CI: 5.1–9.3%). Australia has the lowest prevalence (1.5%,
95% CI: 0.7-2.4%) and Belgium has the highest prevalence (16.6%, 95% CI: 10.7-22.4%),
followed by Canada (14.8%, 95% CI: 9.4–20.1%) and the US (13.0%, 95% CI: 8.3-17.7%).
(6) In 2016, the World Health Organization noted the prevalence of diabetes in Indonesia
was 7% of the total population. Since 1980, the prevalence of diabetes in Indonesia has
Corresponding Author: continued to increase. The percentage of diabetic ulcers as a complication of diabetes
Sukmawati Tansil Tan mellitus in 2011 at RSUP Dr. Cipto Mangunkusumo Jakarta (RSCM) is 8.70%. [7].
Departement of Dermato-
The rate of wound healing in chronic wounds, especially Diabetic foot ulcers (DFU), is very
Venerology, Tarumanagara
University, Jakarta, Indonesia low [8]. has a significant impact on the health and quality of life of patients and their families.
The effect that is often felt is ranging from pain, loss of function and mobility, depression,

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difficulty and anxiety, shame, social isolation, the financial intervention with a closed wound accompanied by scarring
burden of extended hospital stays and chronic morbidity or without secondary side effects. Symptoms of side effects
even death [9]. Previous studies have proven that chronic were not found during the intervention. Treatment during
ulcers are a significant burden and often make the quality of the intervention is the only treatment with injection of
life of their sufferers very poor. Therefore, it is essential to insulin and secretome gel from Placental Wharton Jelly
perform wound care and management of chronic ulcers that Stem Cell (SC-PWJSC) accompanied by regular blood sugar
are efficient and inexpensive to improve the quality of life control for which the regulated dose of diabetes mellitus is
of people with diabetic foot ulcers [8, 10, 11] treated. (Figures 5 and 6)
This case report explains that the potential use of single
dose intracutaneous injection of the secretome from
Placental Wharton Jelly Stem Cell (SC-PWJSC) to patients
with diabetic foot in the lower extremities. Diabetes foot
care in these patients follows the applicable diabetes foot
management protocol with the addition of Secretome from
Placental Wharton Jelly Stem Cell (SC-PWJSC) an
additional therapy to trigger better-wound healing or we
suggest as a gold standard therapy in wound management.

2. Case Report
A 64-year-old man came with complaints of wounds that
have not healed in the right big toe since the last year and
have worsened over the past seven months. Patients have
been advised to undergo finger amputation surgery by a
surgeon to prevent infection, and the finger is predicted to
be untenable. Patients visit to start alternative therapies
using single dose intracutaneous injection of secretome from Fig 1: A grade 3 diabetes foot ulcer
Placental Wharton Jelly Stem Cell (SC-PWJSC)
Past medical history was found that patients have had type 2
diabetes mellitus for more than ten years. Sugar levels are
not well controlled with Glibenklamid treatment. History of
high blood pressure is denied; the history of stroke is
denied. The patient denies a history of haematology
disorder, denied heart and kidney diseases.
The patient current subjective complaint is discomfort in the
legs accompanied by pain, delayed chronic wound healing,
discharge and unpleasant odor form the wound. The patient
also complained of numbness in the toes, especially in the
right big toe. Patients routinely use Povidone iodine to clean
the wound to prevent infection and unpleasant odors.
On physical examination found a grade 3 diabetes ulcer.
The neovascular status around the wound is a blackish blue
wound with CRT prolonged in the wound and cold areas
accompanied by local anesthesia in the wound area. (Figures
1 and 2)
Patients signed up the agreement to follow treatment using
Fig 2: The neovascular status around the wound is a blackish blue
single dose intracutaneous injection of secretome from with prolonged CRT and cold areas accompanied by local
Placental Wharton Jelly Stem Cell (SC-PWJSC) and control anesthesia in the wound area
routinely for two weeks. Patients were also given secretome
gel from Placental Wharton Jelly Stem Cell (SC-PWJSC) to
be applied every day after the wound was cleaned with
NaCl. Patients are also asked to note the symptoms of side
effects that may arise from allergic reactions such as itching,
redness, burning sensation, and swelling to seek first aid if
severe side effects appear that are very disturbing.
The patient came back to control one week later; granulation
tissue began to appear, the bluish color was reduced, dead
skin tissue was whitish around the wound, visible dead
tissue in the wound pushed out of the wound hole. The
patient's neovascular status also improved from the first day
of visit with the color around the bluish-red wound, but
anesthesia still occurred. Patients reported being satisfied
with development for one week in the absence of significant
side effects. (Figures 3 and 4)
The patient came back to control after three weeks of Fig 3: The bluish color was reduced

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Fig 6: A closed wound accompanied by scarring

Fig 4: Granulation tissue began to appear; the bluish color was 3. Discussion
reduced, dead skin tissue was whitish around the wound, visible Stem cell therapy is a new therapy that brings new hope to new
dead tissue in the wound pushed out of the wound hole wound healing methods and is following the physiology of
wound healing in general. These stem cells contain growth and
healing factors to repair wounds [12]. This wound healing
process through the process of withdrawing cells that are not
differentiated into the matrix by healing factors and induce cell
division to close the wound. On the other hand, these stem cells
also play a role in immunomodulation through cytokine
suppression, suppressing inflammation, interacting with
macrophage regulators. This whole process impacts on tissue
regeneration, new capillary growth (angiogenesis) and
accelerates the process of epithelialization in chronic wounds
so that healing occurs as before [13, 14].
One form of stem cells is Mesenchymal stem cells (MSCs),
which can be isolated or obtained from various types of
original tissue [15]. In general, mesenchymal stem cells (MSCs)
can be harvested from placental tissue and its derivatives such
as umbilical cord, newborn skin, and placenta [16, 17]. Planting or
using Mesenchymal stem cells (MSCs) in damaged tissue sites
(locations of chronic ulcers) will support angiogenesis and
vasculogenesis while modulating the immune system. This
whole process plays a vital role in the process of wound
Fig 5: A closed wound accompanied by scarring healing, especially chronic ulcers (Figure 7) [18].

Fig 7: Mechanisms of Angiogenesis and Vasculogenesis in the Treatment of Chronic Ulcers [19]

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The process of wound healing using Mesenchymal stem liver, bone, pancreas, fat components, blood vessels to the
cells (MSCs) is a process that resembles the physiology of skin.(22) MSCs produced from WJ-MSCs in the extracellular
wound healing in general, which starts from Mesenchymal space release several angiogenic factors including basal
stem cells (MSCs) will differentiate into fibroblast and fibroblast growth factor (bFGF) and VEGF which alter beta-
pericytes tissue and form endothelial-like tissue or cells growth factor (TGF-β), PDGF, ANG-1, placental growth
which further play a role in vasculogenesis [20, 21]. Previous factor (PIGF), IL -6, hepatocyte growth factor (HGF), and
literature researches reveal that Wharton's Jelly derived monocyte one chemoattractant protein (MCP-1), which
mesenchymal stem cells (WJ-MSCs) have a rich stimulates angiogenesis in vitro and in vivo [22]. VEGF and
composition of undifferentiated cells that have excellent TGF-β1 secreted in CM promote angiogenesis and activate
nontumorigenic and immunomodulatory properties and do the PI3K/Akt and MAPK pathways; HGF shows its
not cause rejection reactions in the allotransplantation angiogenic nature by inducing VEGF expression [19].
process in repairing organs major such as heart, cartilage,

Fig 8: The schematic perspective of stem cells in skin wound healing and as potent secretome units at different response levels (23)

The use of MSC which is rich in secretome topically in the chronic ulcers but also can be used for various other
field of regenerative medicine has several primary medical fields such as acute wounds, cerebral ischemia
advantages from the provision of stem cells by other and myocardial.
methods, namely 7. It is flexible and can be used as a therapeutic
1. The use of secretomes has excellent safety compared to application and can be modified for various types of
live cell transplantation directly (invasive). cells as desired [23].
2. Secretors originating from MSC is always evaluated for
its safety, dosage, and potential. Conditioned Media (CM) is an ideal environment and has a
3. Topical MSC has a function or efficacy that is no less variety of elements that play a role in storing various
effective than invasive administration, including regeneration factors of cell tissue and tissue. Dissolved
modulating the immune system, angiogenesis, and components consisting of microvesicles and secretomes can
wound healing. be separated singly by multiple methods. The method that
4. Easy storage and can last for a long time without can be used to divide it in the form of microvesicle fraction
decreasing efficacy or even being toxic. consisting of various stages, namely centrifugation,
5. Secretome originating from Wharton's Jelly-derived filtration, polymer-based deposition methods, ion exchange
mesenchymal stem cell (WJ-MSCs) umbilical cord has chromatography, and size-based chromatography. All
economic and practical value and can be mass- elements in Conditioned Media (CM) related to tissue repair
produced under standard laboratory control. and regeneration independently and induced the occurrence
6. Umbilical cord Wharton's Jelly derived mesenchymal of organogenesis de novo and ex vivo tissue [24].
stem cells (WJ-MSCs) can not only be used for healing

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Fig 9: This scheme shows the summary of Mechanism-secretome from Placental Wharton Jelly Stem Cell (SC-PWJSC) in enhancing
diabetic wound healing in every step of the wound healing process

This case report demonstrates the excellent expectation Patients have been advised to undergo finger amputation
result without side effects by using a single dose surgery by a surgeon to prevent infection, and the finger is
intracutaneous injection of the secretome from Placental predicted to be untenable. The intervention was carried out
Wharton Jelly Stem Cell (SC-PWJSC) therapy that is very in the form of the wound injected with a single dose
easy and can even be applied independently to patients with intracutaneous injection of the secretome from Placental
promising outcomes and reduces future disability. In the Wharton Jelly Stem Cell (SC-PWJSC) around the wound.
future, this research can be carried out on a large scale in Patients were also given SC-PWJSC gel to be applied every
Indonesia, starting with serial case reports, clinical trials, day after the wound was cleaned with NaCl. After three
and randomized controlled trials (RCTs). weeks of intervention with a closed wound accompanied by
scarring without secondary side effects. Patients reported
4. Conclusion being satisfied with this treatment.
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