Therapeutic Potential of Stem Cell Conditioned Medium on Chronic Ulcer Wounds
Condition: Chronic Ulcer
MeSH terms: Ulcer
Study type: Interventional
Phase: Phase 1

Summary: 
      Chronic wounds (CW) still represents a heavy burden to many patients and health care
      institution. Despite the most recent advances in wound management, up to 50% of chronic
      wounds still fail to heal. Conventional treatment of chronic wounds does not seem to work in
      several cases, consumes enormous amount of money and time, so it is necessary to develop
      different strategies. Previous studies have reported stem cells ability in tissue
      regenerations due mainly to its secreted paracrine factors, rather than its differentiation
      ability to become new cells. The factors is called secretomes, microvesicles, or exosomes,
      that can be found in the medium where the cells are growing, therefore it called conditioned
      medium (CM). Mesenchymal stem cells (MSCs) such as Wharton's Jelly Mesenchymal Stem Cells
      (WJ-MSC) appear to emerge as a promising wound healing therapy. To the best of investigator's
      knowledge, after conducted a pilot study using animal model to gain the preliminary data for
      the ulcer healing potential, this is the investigator's first clinical study to see the
      therapeutic potentials of Conditioned Medium Stem Cell as an additional growth factors in
      chronic skin ulcer healing and to compare the success of chronic ulcer healing in patients
      undergoing CM treatment and standard approach. The investigators will examine the therapeutic
      effect of human WJ-MSC-CM in wound healing on patients with chronic skin ulcer.
    

Detailed description: 
      Treatment for chronic wound healing has become a great challenge in medical world. The
      incidence of chronic non healing wounds continues to increase and the classical method for
      wound healing therapy no longer reliable for chronic wounds healing. Therefore a new
      alternative strategy to control chronic wound healing is needed. Stem cell therapy has become
      a leading alternative strategy for wound healing therapy in this new modern world. The
      development of using conditioned medium such as Wharton's Jelly Mesenchymal Stem Cells have
      arising because of its paracrine factors that can provide a better healing process. During
      daily practice at the clinic, the authors sometimes find patients with chronic skin ulcers
      that cannot be treated using standard therapy. This encourages the authors to innovate new
      therapy to help the wound healing process by using human WJ-MSC conditioned medium.

      This study has several purposes, such as; to observe the success rate, the differences in the
      period of time needed, and the differences in wound closure of chronic ulcer healing in
      patients undergoing wound care with conditioned medium and standard therapy. As for the
      benefits of research, these are the benefits; reducing the cost spent on treatment in chronic
      skin ulcer, faster chronic wound healing while minimizing the complications, improving the
      quality of therapy for patients with chronic skin ulcers, reducing the treatment period for
      chronic skin ulcer and can be used as the basis for future researchers to conduct further
      research on Conditioned Medium Stem Cell and chronic wound management.

      Stem cell therapy constitutes a new alternative methods of wound healing. Many researchers
      are relying on this alternative new therapy that holds great potentials for its growth
      factors. Mesenchymal stem cell (MSCs) have been isolated from many types of adult tissues and
      fetal tissues, such as umbilical cord, skin, and placenta. When engrafted at sites of tissue
      injury, MSCs differentiate into connective tissue elements, support vasculogenesis, and
      secretes cytokines and growth factors that facilitate healing. As in wounds, MSCs
      differentiate into fibroblasts and pericytes and, perhaps, endothelial-like or vessel
      attached cells. WJ-MSCs secrete proangiogenic and wound healing promoting factors, such as
      transforming growth factor beta (TGF-β), vascular endothelial growth factor (VEGF),
      platelet-derived growth factor, insulin-like growth factor-I, interleukin (IL)-6 and IL-8.

      The use of MSC-sourced secretome in regenerative medicine provides key advantages over
      stem-cell based applications such as; (a) resolving several safety considerations potentially
      associated with the transplantation of living and proliferative cell populations, (b) can be
      evaluated for safety, dosage and potency, (c) storage can be done without application of
      potentially toxic cryopreservative agents for a long period without loss of product potency,
      (d) using MSC-sourced secretome, such as conditioned medium (CM), is more economical and more
      practical for clinical application since it avoids invasive cell collection procedures, (e)
      the time and cost of expansion and maintenance of cultured stem cells could be greatly
      reduced, (f) finally, the biological product obtained for therapeutic applications could be
      modified to desired cell-specific effects.

      This research is an experimental clinical trial with open label. This research will be
      conducted in Sitanala Village (RW 001), Mayapada Hospital, Indra Clinic and Sukma Clinic,
      Banten. Conditioned Medium Stem Cell obtained from SCI (PT. Kalbe Farma, Tbk.). The study
      started from June 2019 to June 2020. The sample used from this study are all outpatient and
      hospitalized patients with chronic skin ulcers at Mayapada Hospital, Indra Clinic, Sukma
      Clinic and Sitanala Village (RW 001) from June 2019 until May 2020. In this pilot study, 38
      subjects will be included based on estimated sample size. The method of selecting samples is
      by using consecutive sampling. Data was collected by measuring the first ulcer and taking
      photos of each subject. The patient then use CM topical therapy and the evaluation is carried
      out after 2 weeks. Results are expressed as means ± SD. The normal distribution of the data
      was assessed using the Shapiro-Wilk test. For multiple comparisons One-Way Analysis of
      Variance (ANOVA) was used. The significance between two independent groups was determined by
      independent Student's t-test and the Mann-Whitney test. An unpaired t-test was performed if
      the data were normally distributed. Otherwise, a Mann-Whitney test was used. Statistical
      analysis was 2-tailed and values were considered statistically significant at p < 0.05.
    

Intervention name(s): Conditioned Media
Intervention type(s): Drug
Intervention description(s): Conditioned Media represents the complete regenerative milieu of cell-sourced secretome and vesicular elements. The soluble components of the secretome may be separated from the microvesicle fraction by centrifugation, filtration, polymer precipitation-based methodologies, ion exchange chromatography and size-exclusion chromatography. Both of these components may be capable of independently triggering regeneration and repair as well as of mediating the de novo organogenesis of tissue-engineered organs ex vivo.
Intervention model: Single Group Assignment
Intervention model description: Experimental clinical trial with open label
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Stem Cell; Conditioned Medium