A Case Report: Role of Human Amniotic Membrane Mesenchymal

Stem Cells-Conditioned Medium (hAMMSC-CM) Combine with

Vitamin E for Treating Chronic Plantar Pedis Ulcer in Leprosy

Patient

Marissa Astari

, Afif Nurul Hidayati

, Medhi Denisa Alinda

, Bagus Haryo Kusumaputra

, Linda

Astari

, M. Yulianto Listiawan

, Indropo Agusni

, Fedik A Rantam

2,3

, Sunarso Suyoso

, Evy

Ervianti

, Linda Astari

, Yuri Widia

, Sylvia Anggraeni

, Cita Rosita Sigit Prakoeswa

Departement of Dermatology and Venereology, Dr. Soetomo Teaching Hospital / School of Medicine,

Universitas Airlangga, Surabaya, Indonesia

Stem Cell Laboratory, Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia

Virology and Immunology Laboratory, Department of Microbiology, Faculty of Veterinary Medicine, Universitas

Airlangga, Surabaya, Indonesia

Keywords: human amniotic membrane stem cells, vitamin E, chronic plantar ulcer, leprosy

Abstract: Leprosy ulcers are mostly present in plantar pedis especially in areas with bony prominance. Plantar ulcers

healimg in leprosy ide often dificult and time comsuming because of the declining of growth factors and

cytokines as a result of a prolonged inflammatory condition. A 70-years old man working as pedicab driver

had an ulcer at his left feet since 2 yaers ago, painless and not itchy. On regio caput metatarsal digiti 1 pedis

sinistra there were 4 x 4 x 0,4 cm with necrotic tissue around. The patient was suffering from borderline

leprosy since 10 years and already finished the treatment without history of drop out. We applied topical

human amniotic membrane mesenchymal stem cells-conditioned medium (hAMMSC-CM) combine with

vitamin E gel for 5 weeks and the ulcer healed completely.

1 INTRODUCTION

Ulcers are loss of continuity of skin tissue up to the

dermis or deeper (subcutis). Approximately 30% of

patients with Leprosy have peripheral nerve damage,

and 10-20% of them have neuropathic ulcers due to

peripheral nerve damage. Leprosy ulcers are mostly

present in plantar pedis especially in areas with bony

prominence. Plantar pedis is a part of the body that

works for walking, so the risk for experiencing

trauma is greater than other body parts

(Diegelmann, 2004). Plantar ulcers healing in

leprosy is often difficult and time-consuming

because of the declining of growth factors and

cytokines as a result of a prolonged inflammatory

condition.

2 CASE

A 70-years old man working as pedicab driver came

with chief complaint ulcer at his left feet since 2

years ago, painless and not itchy. At first the ulcer is

small and getting bigger and never healed. On regio

caput metatarsal digiti 1 pedis sinistra there were

ulcus 4 x 4 x 0,4 cm, with necrotic tissue around.

The patient was suffering from borderline

leprosy since 10 years ago. He had already got

multibacillary multi-drug therapy for 12 months and

had finished the treatment without history of drop

out. The result of microbiology Mycobacterium

leprosy examination was bacterial index (BI) 0 and

morphological index (MI) was negative.

The initial treatment for the ulcer was sterile

normal saline and surgical debridement to remove

necrotic tissue, callus, and debris. After obtaining a

clean ulcer, wound area and wound depth

measurements were performed. Then the ulcer was

Astari, M., Hidayati, A., Alinda, M., Kusumaputra, B., Astari, L., Listiawan, M., Agusni, I., Rantam, F., Suyoso, S., Ervianti, E., Astari, L., Widia, Y., Anggraeni, S. and Prakoeswa, C.

A Case Report: Role of Human Amniotic Membrane Mesenchymal Stem Cells-Conditioned Medium (hAMMSC-CM) Combine with Vitamin E for Treating Chronic Plantar Pedis Ulcer in

Leprosy Patient.

DOI: 10.5220/0008160504930495

In Proceedings of the 23rd Regional Conference of Dermatology (RCD 2018), pages 493-495

ISBN: 978-989-758-494-7

493

given framycetin gauze dressing (FGD) and sterile

gauze above the FGD. On subsequent visit, the

ulcers begin to be given topical hAMMSC +

Vitamin E gel and covered with transparent film

dressings. Application of gel was done every 3 days,

and weekly evaluation included measurement of the

size and the depth of the ulcer was done. Initial

measurements of the ulcer was 4x4x0.4 cm. Patient

received hAMMSC + vitamin E gel for 5 weeks.

After the therapy with hAMMSC + Vit C gel for 5

weeks, the ulcer healed compeletely.

Figure 1: (A) After debridement and first application of hAMMSC + vitamin E (B) After 2 weeks of application (C) After 3

weeks of application (D) After 4 weeks of application (E) After 5 weeks of application and the ulcer completely healed.

3 DISCUSSION

We present a case of chronic plantar pedis ulcer in

leprosy patient that could completely healed with

topical gel combination of hAMMSC-CM and

vitamin E. Plantar ulcers in MH are neuropathic

ulcers, occurring due to prior nerve damage or

sequelae. Chronic ulceration results from one or

more extinctions of the wound healing phase.

(Diegelmann, 2004) In a chronic wound, one may

detect a prolonged inflammatory response, elevated

protease activity and decreased growth factors.

These findings may account for the delayed wound

healing process. The prolonged inflammatory

response may be caused by infection or just

inflammation. The FGD is an antibiotic wound

dressing that works in the inflammatory phase of

wound healing by treating the infection and contra-

acting the colonisation. It is not effective in an

inflammatory phase of wound healing that is not

caused by infection. It is also not effective in the

proliferative phase of wound healing.(Ennis et al.,

2013; Nuschke, 2014)

Studies on the human amniotic membrane

mesenchymal stem cells (hAMMSC) for the repair

and regeneration of cells showed good results. The

growth factors and cytokines can be found in the

tissue medium of stem cells in in vitro conditions

through its metabolite product so it can be utilized as

a useful modality in the process of cell

regeneration.(Jayaraman et al., 2013; Maxson et al.,

2012)

The previous research has proved that injuries

that are difficult to heal in humans have high levels

of oxidative stress. Wounds or chronic ulcers often

show the increasing levels of reactive oxygen

species (ROS) or free radicals that can delay wound

healing process, inhibit the formation of granulation

tissue and epithelialization. Free radicals are formed

in response to tissue damage which then inhibits the

recovery process by attacking DNA, membranes,

proteins, and lipids from cells. Antioxidants are

believed to repair wounds by reducing the damage

caused by free radicals released by neutrophils in the

inflammatory phase of the wound healing

process. (Moro, 1999; Telang, 2013)

The hAMMSCs contains many cytokines and

growth factors, which may be effective in the

inflammatory and the proliferation phase of the

wound healing. In the inflammatory phase of wound

healing, the pro-inflammatory cytokines in

hAMMSCs may influence the infection and

colonisation via its antimicrobial effect and the anti-

inflammatory cytokines in hAMMSCs will diminish

the inflammation (immunomodulatory effect). In the

proliferation phase of the wound healing, the growth

factors in hAMMSCs will stimulate proliferation

and migration of cells, induce angiogenesis, and

stimulate the formation of tissue granulation and

epithelialization. (Jayaraman et al., 2013; Maxson et

al., 2012)

Vitamin E is a non-enzymatic natural antioxidant

and the most important lipid soluble in human tissue

which is absorbed by the skin well. Several studies

RCD 2018 - The 23rd Regional Conference of Dermatology 2018

494

have shown that vitamin E, especially a-tocopherol,

gives good results in the wound healing

process. Alpha tocopherol may serve as an

antioxidant, reducing ischemic damage due to

reperfusion disorders, may stimulate growth and

stabilize the granulation tissue, as well as re-

epithelialization.

Prakoeswa et al. (2018), study analytical

experimental approach comparing the topical

hAMMSC-CM and the framycetin gauze dressing

(FGD) applied every 3 days up to 8 weeks on the

healing of chronic plantar ulcer of leprosy. Ulcer

healing in the hAMMSC-CM group was

significantly better than that in the FGD group was

significant clinical and statistical differences

(p<0.005 and p<0.005).

4 CONCLUSIONS

In this study we found that hAMMSC-CM

combination with Vitamin E may imrpove healing of

chronic plantar ulcer of leprosy.

REFERENCES

Diegelmann, R.F., 2004. Wound healing: an overview of

acute, fibrotic and delayed healing. Frontiers in

Bioscience 9, 283.

Ennis, W.J., Sui, A., Bartholomew, A., 2013. Stem Cells

and Healing: Impact on Inflammation. Advances in

Wound Care 2, 369–378.

Jayaraman, P., Nathan, P., Vasanthan, P., Musa, S.,

Govindasamy, V., 2013. Stem cells conditioned

medium: A new approach to skin wound healing

management. Cell Biology International 37, 1122–

1128.

Maxson, S., Lopez, E.A., Yoo, D., Danilkovitch-

Miagkova, A., LeRoux, M.A., 2012. Concise Review:

Role of Mesenchymal Stem Cells in Wound Repair.

STEM CELLS Translational Medicine 1, 142–149.

Moro, O., 1999. Biological Activities of a Stable Ascorbic

Acid Derivative , Acid ( Aa-2G ) in Cosmetics.

Journal of Applied Cosmetology 18, 154–163.

Nuschke, A., 2014. Activity of mesenchymal stem cells in

therapies for chronic skin wound healing.

Organogenesis.

Telang, P., 2013. Vitamin C in dermatology. Indian

Dermatology Online Journal 4, 143.

Prakoeswa CRS. Efficacy of topical human amniotic

membrane mesenchymal stem cell-conditioned

medium (hAMMSC-CM) on the healing of chronic

plantar ulcers in leprosy:a controlled prospective

clinical trial (in press)

A Case Report: Role of Human Amniotic Membrane Mesenchymal Stem Cells-Conditioned Medium (hAMMSC-CM) Combine with

Vitamin E for Treating Chronic Plantar Pedis Ulcer in Leprosy Patient

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