Subcutaneous and Intravenous Administration of Human Umbilical Cord Mesenchymal Stem Cells in Patient With Multiple Foot Ulcers Complicated by Scleroderma

Subcutaneous and Intravenous Administration of Human Umbilical Cord Mesenchymal Stem Cells in Patient With Multiple Foot Ulcers Complicated by Scleroderma- A Case Report with One Year Follow Up

Megha Patel¹, Ankur Patel¹, Prashant Kshatriya^1*

¹Senior Scientist, Viecell Institute of Regenerative Medicine Surat, India

*Correspondence author: Prashant Kshatriya, Senior Scientist, Viecell Institute of Regenerative Medicine Surat, India; Email: prashant@viecells.com

Published Date: 04-10-2023

Copyright^© 2023 by Kshatriya P, et al. All rights reserved. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

We treated a patient with progressive, refractory scleroderma with multiple ulcers on her feet with a combination of intravenous and a subcutaneous injection at the periphery of the ulcers using Umbilical Cord-Derived Mesenchymal Stem Cells (UCMSCs). The patient improved subjectively and objectively and we have followed up with the patient for 1 year. The combination was well tolerated and effective, suggesting a large-scale study may be warranted for progressive, refractory scleroderma ulcer treatment.

Keywords: Mesenchymal Stem Cells (MSCs); Scleroderma; Ulcer

Introduction

The word “scleroderma” means hardening of skin and that is the most visible symptom of the complaint [1,2]. Scleroderma is an autoimmune disease whose etiology remains unknown affecting the connective tissues, characterized by vascular complaint which further leads to increased collagen and extracellular matrix deposit, fibrotic concession, ulcer and inflammation of the skin and affects internal organs like lungs, digestive tract, blood vessel, heart [3]. All these symptoms are responsible for increased morbidity and lead to functional disability (like reduced mouth opening and loss of hand function), pain and cerebral consequences. This impacts not only the patient’s quality of life but also reduces his life expectation. In at least half of the cases, patient will die from Systemic Sclerosis (SSc)- related diseases and the other half from advanced prevalence of malice and cardiovascular conditions compared to the general population [4,5]. There’s no restorative treatment to date. Only characteristic treatments are generally proposed to patients to palliate pain and ameliorate function. New remedial strategies are being imaged among which Mesenchymal Stem Cells (MSCs) grounded remedy, which is presently under evaluation in the conventions.

Properties of Mesenchymal Stem Cells (MSCs)

MSCs are adult multipotent progenitor cells, which have been first isolated from bone marrow [5]. In addition to bone marrow derived MSCs (BM-MSCs) now they have been isolated from several tissues, including Adipose Tissue (ASCs), umbilical cord (UC-MSCs), placenta (PD-MSCs) or dental pulp [6]. MSCs are defined by 3 criteria, as proposed by the International Society for Cell Therapy: (a) plastic adherence, (b) the positive cell surface markers CD73, CD90, CD105 and lack of expression of the hematopoietic markers CD34, CD45, HLA-DR and (c) capacity of differentiation into adipocytes, chondrocytes and osteoblasts [7]. Along with their potential of multilineage differentiation, MSCs shows several paracrine functions like they support survival and differentiation of hematopoietic stem cells, induce cell proliferation and have anti-fibrotic, antiapoptotic, pro-angiogenic, anti-bacterial and anti-inflammatory effects [8]. Although MSCs from different tissue sources share similar properties, they may display some differences in their immunomodulatory capacity or differentiation potential [9,10].

Mechanism of mesenchymal stem cells in counteracting scleroderma symptoms

MSCs are proposed to play important roles in several diseases via different mechanisms of action, in which various mediators are also secreted through each of these mechanisms [12,13]:

• The anti-fibrotic property prevents collagen accumulation in the skin, lung and digestive system [12,14]
• The angiogenic properties go against widespread vasculopathy by using Vascular Endothelial Growth Factor (VEGF), Insulin-Like Growth Factor-1 (IGF-1), HGF, Platelet-Derived Growth Factor (PDGF) and IL6 [12,14]
• The anti-inflammatory property counteracts the dysregulation of the immune system. TGFβ1, IL6, Prostaglandin E2 (PGE2), HGF, Interferon-Gamma (IFN-γ), IL- 10, IL4, Tumor Necrosis Factor alpha (TNF-α), Glucocorticoid-Induced Leucine Zipper (GILZ), Indolamine-2,3-Dioxygenase (IDO) and inducible NO Synthase (iNOS) are associated with this mechanism [15-18]

Method

The patient had their complaint verified by at rheumatologists. The stem cell injection procedures were fully explained. Patient had inked written informed consent. Umbilical Cords (UCs) were used as a source of the allogenic MSCs. The UCs were used within 2 h of delivery. The cords are cleaned with 70% alcohol also washed completely with saline and digested mechanically and enzymatically with collagenase I under sterile conditions. The dissolved cord was gathered and suspended in the growth medium. The digested cord was placed in 6-well plates and dressed in Dulbecco’s Modified Eagle’s Medium (DMEM) (Sigma, Germany), supplemented with 10 (v/ v) Fetal/ Bovine Serum (FBS) (Sigma, Germany), 2 mM L- glutamine, 100 U/ mL penicillin, 100 mg/ mL streptomycin and 1 µg/ mL amphotericin B (Lonza, Belgium). The culture plate was placed in an incubator with impregnated moisture at 5% CO₂ at 37 ℃. The medium was changed doubly weekly till 80% confluency was reached. The cells were detached with trypsin, counted and seeded in vented tissue culture flask (Corning, USA) until passage [4]. Eventually, the cells were detached, counted and washed and suspended in the normal saline for intravenous infusion. A stem cell injection was given on the fringe of ulcer subcutaneously using insulin hype. The 3 cycles are given at the interval of 30 days (Fig. 1-4).

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