Effectiveness of Secretome from Human Umbilical Cord Mesenchymal Stem Cells in Gel (10% SM-hUCMSC Gel) for Chronic Wounds (Diabetic and Trophic Ulcer) – Phase 2 Clinical Trial

Abstract

Background

Chronic wounds carry financial burdens and increase morbidity and mortality, especially in diabetic ulcers and Hansen’s Morbus. More than 50% of chronic ulcers are difficult to heal with regular treatment and require new types of therapy such as the use of secretome of human umbilical cord mesenchymal stem cells (SM-hUCMSC).

Methods

This experimental study was carried out to see the effectiveness of using SM-hUCMSC in diabetic ulcers and Hansen’s Morbus in four medical facilities (multicentre). The level of active secretion has been measured by default in 10% SM-hUCMSC gel, used as a treatment intervention. The primary outcome is wound healing in terms of the length, width, and extent of the wound. The secondary is the side effects of treatment 2 weeks after administration. Follow-up visits will be scheduled at 1 and 2 weeks post-treatment.

Results

Forty-one chronic ulcers successfully followed the study until the end. In patients with chronic ulcers, the mean ulcer length, width, and area were 1.60 (0,50–13,0), 1.3 (0,5–6,0), and 2.21 (0,25–78) cm square, respectively, before interventions and 1 (0–12), 0,8 (0–6,0), and 1 (0–72) square cm after interventions at the second follow-up. The change between the beginning and end of the intervention was significant (p-value <0.05).

Conclusion

The use of 10% SM-hUCMSC gel topically has been proven effective in accelerating the process of wound healing, especially chronic ulcers with side effects that are not present in this study.

Keywords:

• chronic wound healing
• secretome of human umbilical cord-derived MSCs gel
• diabetic chronic ulcers
• leprosy

Abbreviation

CM-hUCMSC, Conditioned Medium of Human Umbilical Cord Mesenchymal Stem Cells; ASC, Adipose-Derived Stromal Cell; b-FGF, Basic Fibroblast Growth Factor; BM-SC, Bone Marrow Stem Cell; CCK-8, Cell Counting Kit-8; CM, Conditioned Media; cm, Centimeter; CNTF, Ciliary Neurotrophic Factor; CTGF, Connective Tissue Growth Factor; ECM, Extracellular Matrix; EGF, Epidermal Growth Factor; ELISA, The Enzyme-Linked Immunosorbent Assay; FGF, Fibroblast Growth Factor; GM-CSF, Granulocyte-Macrophage Colony-Stimulating Factor; HaCaT, Human Keratinocyte; HGF, Hepatocyte Growth Factor; hMSC, Human Mesenchymal Stem Cells; HTS, Hypertrophic Scars; hUC-MSC, Human Umbilical Cord Mesenchymal Stem Cells; IFN, Interferon; IGF, Insulin-Like Growth Factor; IGFBP, Insulin-Like Growth Factor Binding Protein; IL, Interleukin; IL18-BP, IL18 binding protein; IL1RA, IL1 receptor antagonist; Kg, Kilogram; KGF, Keratinocyte Growth Factor; MMP, Matrix Metalloproteinase; MSC, Mesenchymal Stem Cells; NT-3, Neurotrophin 3; PDGF, Platelet-Derived Growth Factor; PGF, Placental Growth Factor; PT SST, Perseroan Terbatas Sukma Skin Treatment; RCT, Randomized Controlled Trial; SC-hUCMSC, Secretome of Human Umbilical Cord Mesenchymal Stem Cells; SC-PWJSC, Secretome From Placental Wharton Jelly Stem Cell; TGF-1, Tumor Growth Factor-1; TNF, Tumor Necrosis Factor; UTHREC, Universitas Tarumanagara Human Research Ethics Committee; VEGF, Vascular Endothelial Growth Factor; WHO, World Health Organization; α-SMA, Alpha-Smooth Muscle.

Data Sharing Statement

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Ethical Clearance

Ethical Clearance for this study was obtained from Universitas Tarumanagara Human Research Ethics Committee Institute of Research and Community Engagement (Register Number: PPZ20192072 and Number of Letter: 1007-Int-KLPPM/Untar/VI/2020). This study has been registered at ClinicalTrials.gov with ID number: NCT04134676.

Inform Consent

Informed consent was obtained from all individual participants included in this study. The purpose and procedures of the study were explained to each participant, including any potential risks or benefits. Participants were informed of their right to withdraw from the study at any time without penalty. Confidentiality of participants’ data was ensured, and all data were anonymized and securely stored. The study protocol was approved by the relevant ethical review board/institutional review board, and the research was conducted in accordance with the principles of the Declaration of Helsinki”.

Acknowledgments

This study has been presented in the form of a grant fund accountability presentation. The authors are grateful to the following individuals for their generous help: Department Research. PT. Sukma Skin Treatment (PT. SST) to help us solve several problems in statistics. Department of Management of PT. Sukma Skin Treatment (PT. SST) for administration and Universitas Tarumanagara Human Research Ethics Committee Institute of Research and Community Engagement for ethics. Thank you to all the Mayapada Hospital, Sitanala Hospital, Indra Clinic, and Sukma Clinic for their permission to carry out this research. Do not forget we also thank all nurses, doctors, and research assistants who have worked together so that this research can be completed properly. We also thank Yuyus Kusnadi, Christine Ayu Lagonda, and Dilafitria Fauza for preparing the human umbilical cord mesenchymal stem cell secretome.

Disclosure

The authors declared that they have no conflicts of interest.

Additional information

Funding

This project was supported by a grant from Institute of Research and Community Engagement Universitas Tarumanagara (Grant/Award Number: 012 Int-DIR.PPKM/ 3). As a kind of internal accountability, the complete methodology and outcomes of this research have been posted to the Tarumanagara University repository.