Abstract
BackgroundCompromised wound healing has become a global public health challenge which presents a significant psychological, financial, and emotional burden on patients and physicians. We recently reported that acellular gelatinous Wharton’s jelly of the human umbilical cord enhances skin wound healing in vitro and in vivo in a murine model; however, the key player in the jelly which enhances wound healing is still unknown.MethodsWe performed mass spectrometry on acellular gelatinous Wharton’s jelly to elucidate the chemical structures of the molecules. Using an ultracentrifugation protocol, we isolated exosomes and treated fibroblasts with these exosomes to assess their proliferation and migration. Mice were subjected to a full-thickness skin biopsy experiment and treated with either control vehicle or vehicle containing exosomes. Isolated exosomes were subjected to further mass spectrometry analysis to determine their cargo.ResultsSubjecting the acellular gelatinous Wharton’s jelly to proteomics approaches, we detected a large amount of proteins that are characteristic of exosomes. Here, we show that the exosomes isolated from the acellular gelatinous Wharton’s jelly enhance cell viability and cell migration in vitro and enhance skin wound healing in the punch biopsy wound model in mice. Mass spectrometry analysis revealed that exosomes of Wharton’s jelly umbilical cord contain a large amount of alpha-2-macroglobulin, a protein which mimics the effect of acellular gelatinous Wharton’s jelly exosomes on wound healing.ConclusionsExosomes are being enriched in the native niche of the umbilical cord and can enhance wound healing in vivo through their cargo. Exosomes from the acellular gelatinous Wharton’s jelly and the cargo protein alpha-2-macroglobulin have tremendous potential as a noncellular, off-the-shelf therapeutic modality for wound healing.
Highlights
Compromised wound healing has become a global public health challenge which presents a significant psychological, financial, and emotional burden on patients and physicians
acellular gelatinous Wharton’s jelly (AGWJ) contains proteins characteristic of exosomes We recently reported that AGWJ treatment of human fibroblasts and keratinocytes in vitro leads to enhanced cell migration of these cells, a key characteristic of skin wound healing [43]
Since acellular Wharton’s jelly showed a beneficial effect on skin healing, and the extracellular matrix holds the Wharton’s jelly, we aimed to identify proteins that exist in AGWJ by performing mass spectrometry on umbilical cord AGWJ
Summary
Compromised wound healing has become a global public health challenge which presents a significant psychological, financial, and emotional burden on patients and physicians. One of the most important functions of the skin is to be a barrier against the environment [1]. Insults such as burns, chronic skin ulcers as a result of pressure, venous stasis, or diabetes mellitus represent some of the conditions in which the tissue integrity is disrupted and a wound is created [1, 2]. Stem cell therapies have received much attention during the last decade, for the management of deficient skin healing. One of the sources of stem cells used for wound healing is the umbilical cord both for deficient healing and, it has been suggested, as a possible remedy for excessive healing [20, 21]. The umbilical cord is a highly promising area of wound healing research
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