The Effect of Conditioned Medium Derived Wharton’s Jelly

Messenchymal Stem Cell for Diabetic Foot Ulcer:

Preeliminary Study – Case Series

Ferry Arrochman, Eva Niamuzisilawati, Nurrachmat Mulianto, Indah Julianto

Dermatovenereology Departement Dr. Moewardi General Hospital/Faculty of Medicine Sebelas Maret University,

Surakarta

Keywords: Wharton’s jelly, diabetic foot ulcer.

Abstract: Diabetic foot ulcer (DFU) is the one of long term complications of diabetes melitus with the life time risk up

to 25%. The patogenesis of DFU is complicated and multifactorial, resulting from the combined effects of

both local and systemic abnormalities. It is a chronic inflamation condition that diabetes melitus it self can

increase vascular complications like perifer neurophaty, vascular permeability cause high compartment and

triger tissue hypoxia. The failure of diabetic fibroblast to produce VEGF disturb neovascularization then

DFU can not recover easily. Topical conditioned medium derived wharton’s jelly as the therapeutic

strategies in regenerative medicine of diabetic foot ulcer. It is an evolution for DFU regeneration.

1 INTRODUCTION

Chronic ulcers are defined as spontaneous or

traumatic lesions, typically in lower extremities that

are unresponsive to initial therapy or that persist

despite appropriate care and do not proceed towards

healing in a defined time period with an underlying

etiology that may be related to systemic disease or

local disorders (Suthar et a., 2017).

Diabetic foot ulcer are the most common medical

complication of patients with diabetes melitus, with

an estimated prevalence of 12-15% in diabetes

melitus patients (American Diabetes Association).

Diabetes mellitus type II (DM2) is a metabolic

disorder defined by hyperglycemia due to insulin

resistance. In diabetes, chronic skin ulcerations are

common on the lower extremities, particularly the

foot (Okonkwo & Dipetro, 2017). The diabetic

patient with foot ulcer require long-term

hospitalization and cary the risk of limb amputation

(Mariam et al., 2017).

Diabetes mellitus–associated impaired wound

healing severely affects life quality of patients

(Dangwal et al., 2015).

The hunt for effective

therapies to treat the sizable patient population

affected by the chronic, non-healing wounds brought

on by diabetes has been elusive. While there has

been research that has progressed from laboratory, to

clinical trials, and finally to clinical practice, these

treatments have failed to be the silver bullet that will

heal chronic diabetic wounds (Dangwal et al., 2015).

Wound healing requires a coordinated interplay

among cells, growth factors, and extracellular matrix

proteins. Central to this process is the endogenous

mesenchymal stem cell (MSC), which coordinates

the repair response by recruiting other host cells and

secreting growth factors and matrix proteins

(Julianto & Dindiastuti, 2016). This study use

messsenchimal conditioned media from

messenchimal punca cell wharton’s jelly. Wharton’s

Jelly is the primitive mucous, connective tissue of

the umbilical cord lying between the amniotic

epithelium and the umbilical vessels. First observed

by Thomas Wharton in 1656, this gelatinous

substance is comprised of proteoglycans and various

isoforms of collagen. The main role of the

Wharton’s Jelly is to prevent the compression,

torsion, and bending of the umbilical vessels which

provide the bi-directions flow of oxygen, glucose

and amino acids to the developing fetus, while also

depleting the fetus and placenta of carbon dioxide

and other waste products (Taghizadeh et al., 2011).

Messenchimal punca cell has a specific character

that is improve and transdiferensiasi it self to

become some cell strain like bone cell, tendo and

myosit. On the other hand messenchimal punca cell

526

Arrochman, F., Niamuzisilawati, E., Mulianto, N. and Julianto, I.

The Effect of Conditioned Medium Derived Wharton’s Jelly Messenchymal Stem Cell for Diabetic Foot Ulcer: Preeliminary Study – Case Series.

DOI: 10.5220/0008161305260528

In Proceedings of the 23rd Regional Conference of Dermatology (RCD 2018), pages 526-528

ISBN: 978-989-758-494-7

can regulate human immunity and inflamation

responses. It is very important for wound healing by

reapair and make inflamation process be faster then

there is no chronic healing (Julianto & Rindiastuti,

2016).

Figure 1: Before treatment.

2 CASE

We reported a preeliminary study - case series taken

from dermatology outpatient clinic Moewardi

hospital Surakarta. The patient is a male 58 years

old who is consulted from an orthopedics with DFU.

He suffered from diabetes melitus since he was 42

year old. He got DFU for a year. His foot fingers,

digiti 2 and 3 has been amputated 6 month ago by

orthopedics. We started treated this patient by

applicated topical conditioned medium derived

wharton’s jelly messenchymal stem cell while the

ortopedics did debridement.

Photographic documentation was performed by

the same investigator and with the same digital

camera immediately before (Figure 1) the procedure

and after (Figure 2) therapy session

3 DISCUSSION

Chronic wounds (CWs) are by definition 'wounds

that have failed to progress through the normal

stages of wound healing and therefore enter a

pathological state of inflammation. As a result, the

healing process is delayed, or incomplete, and does

not proceed in a coordinated manner, subsequently

resulting in a poor anatomical and functional

outcome (Abbott et al., 2005).

With respect to diabetes, patients with the

disease have a 12-25 % lifetime risk of developing a

diabetic foot ulcer (DFU) (Singh et al., 2005;

Johansson et al., 2008). and 5-8 % require

amputation within 1 year (Johansson et al., 2008;

Pompers et al., 2008). In fact complications of DFUs

are the primary cause of non-traumatic lower

extremity amputations with DFUs preceding

approximately 85 % of such amputations.

Furthermore amputation secondary to DFUs is

associated with a high morbidity and mortality rate,

with a survival rate as low as 31 % for major limb

amputees (Larsson et al., 1998; Miyajima et al.,

2006).

SC-CM has a wide range of cytokines and GF

related directly to the wound healing process (Table

1). The next phase of recovery involves

angiogenesis, whereby molecules such as VEGF,

bFGF, EGF and TGF-b promote new blood vessel,

sustain the newly formed granulation tissues and

help in the survival of endogenous keratinocytes. In

the late phase of the wound healing process, GFs

such as EGF, GM-CSF and hepatocyte GF (HGF)

prompt keratinocytes to migrate from the basal

population around the wound edge to cover the

lesion and differentiate into squamous keratinizing

epidermal cells (Metcalfe & Ferguson, 2007).

4 CONCLUSION

Then after treatment we can report that Topical

conditioned medium derived wharton’s jelly

messenchymal stem cel is an evolution which can

regenerate diabetic foot ulcer very well.

Figure 2: After treatment.

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