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June 26, 2023 at 4:28:44 AM

Wound Healing

Accelerating Healing: How Stem Cell Culture Supernatant Revolutionizes Wound Repair

Wound Healing

Wound Healing can be generally categorized into two contexts. Medicine and Beauty.

In the context of science and medicine:

Healing refers to the process by which the body repairs and restores damaged or injured tissues to their normal state. It is a complex physiological process that involves a series of coordinated events at the cellular and molecular levels. When an injury occurs, the body initiates a response aimed at stopping bleeding, removing debris, and preventing infection. This initial phase is called the inflammatory phase, characterized by increased blood flow, release of chemical mediators, and migration of immune cells to the site of injury. Following the inflammatory phase, the proliferative phase begins, during which new blood vessels form, and cells such as fibroblasts produce collagen to rebuild the damaged tissue. This phase also involves the regeneration of new skin cells and the formation of a scar if necessary. Finally, the remodeling phase occurs, where the newly formed tissue gradually gains strength and flexibility. The scar tissue undergoes remodeling to improve its function and appearance, although it may not be identical to the original tissue.

Healing is important in the field of science and medicine for several reasons:

1. Restoration of function: Healing enables the body to repair injured tissues and regain normal function. This is vital for restoring mobility, organ function, and overall well-being.

2. Prevention of infection: The healing process involves the activation of the immune system, which helps to fight off pathogens and prevent infection at the site of injury.

3. Maintenance of homeostasis: Healing helps maintain the body's internal balance and stability by repairing damaged tissues and restoring their normal structure and function.


In the context of beauty and anti-aging, healing refers to the rejuvenation and repair of the skin to promote a more youthful and healthy appearance. Skin healing is essential for addressing various aesthetic concerns, such as wrinkles, scars, and discoloration. The skin has a remarkable ability to heal itself through the process of skin renewal. This process involves the shedding of old skin cells and the production of new ones, resulting in a refreshed and more youthful complexion. However, as we age, the skin's natural healing processes can become less efficient.

Healing in the context of beauty and anti-aging is important because it can:

1. Reduce the appearance of wrinkles and fine lines: By stimulating collagen production and enhancing skin renewal, healing processes can help diminish the visible signs of aging, leading to a smoother and more youthful complexion.

2. Improve skin texture and tone: Healing can help minimize the appearance of scars, age spots, and uneven skin tone, resulting in a more even and radiant complexion.

3. Boost self-confidence: By improving the appearance of the skin, healing interventions in the context of beauty and anti-aging can have a positive psychological impact, boosting self-esteem and confidence.

Wound Healing and the world of Regenerative Science.

Acalah's Stem Cell culture supernatant has proven to be a remarkable advancement in the field of wound healing, displaying potent benefits. Extensive research and clinical trials have demonstrated its remarkable ability to accelerate the healing process and enhance tissue regeneration. The unique combination of growth factors, cytokines, and extracellular matrix components present in Acalah's Stem Cell culture supernatant contributes to its impressive therapeutic effects. This innovative solution not only promotes the proliferation and migration of various cell types crucial for wound healing, but it also stimulates the production of new blood vessels, leading to improved oxygenation and nutrient supply to the damaged tissue. Moreover, Acalah's Stem Cell culture supernatant has exhibited anti-inflammatory properties, reducing inflammation and preventing infection in the wound site. With its proven efficacy and safety, Acalah's Stem Cell culture supernatant has emerged as a promising solution for optimizing wound healing outcomes, offering hope for individuals seeking effective and efficient treatment options.


Promotion of cell proliferation and migration: 

Stem cell culture supernatant contains growth factors such as epidermal growth factor (EGF), transforming growth factor-beta (TGF-β), and basic fibroblast growth factor (bFGF), which have been shown to promote the proliferation and migration of various cell types involved in wound healing (Li et al., 2012; Zhang et al., 2015). For example, EGF has been found to stimulate keratinocyte proliferation and migration, contributing to reepithelialization of the wound (Anitua et al., 2015). TGF-β can induce fibroblast proliferation and collagen synthesis, aiding in the formation of new connective tissue (Barrientos et al., 2008).


Modulation of the inflammatory response: 

Several studies have demonstrated that stem cell culture supernatant contains anti-inflammatory factors that can modulate the immune response during wound healing. The presence of factors such as interleukin-10 (IL-10) and hepatocyte growth factor (HGF) in stem cell culture supernatant has been shown to reduce pro-inflammatory cytokine production and attenuate inflammatory processes (Roemeling-van Rhijn et al., 2013; Sohni et al., 2017). These anti-inflammatory effects help prevent excessive inflammation, which can hinder the healing process.


Stimulation of angiogenesis: 

Stem cell culture supernatant has been found to promote angiogenesis, which is crucial for efficient wound healing. Factors such as vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and angiopoietin-1 (Ang-1) present in stem cell culture supernatant have been shown to induce endothelial cell proliferation, migration, and tube formation, thereby enhancing the formation of new blood vessels (Hou et al., 2014; Wang et al., 2017). In a study using a diabetic wound model, application of conditioned media from adipose-derived stem cells improved wound healing and increased angiogenesis (Li et al., 2016).


Enhancement of extracellular matrix production:

Stem cell culture supernatant contains factors that can promote the synthesis and remodeling of the extracellular matrix, which is essential for proper tissue repair. Growth factors like TGF-β and bFGF present in stem cell culture supernatant can stimulate fibroblasts to produce collagen, elastin, and other ECM components (Zhang et al., 2015; Hou et al., 2014). In a study using a full-thickness skin defect model, application of conditioned media from human umbilical cord mesenchymal stem cells promoted collagen deposition and accelerated wound healing (Wu et al., 2017).


Immunomodulatory effects:

Stem cell culture supernatant exhibits immunomodulatory properties that can influence the immune response at the wound site. Studies have shown that stem cell culture supernatant can regulate the activity of immune cells, such as macrophages and T cells, leading to a more favorable healing environment (Ankrum et al., 2014; Li et al., 2012). For instance, conditioned media from bone marrow mesenchymal stem cells has been shown to reduce the production of pro-inflammatory cytokines by macrophages and enhance their phagocytic activity (Gao et al., 2016).

History of Wound Healing

The history of wound healing research in the field of regenerative medicine is a fascinating journey marked by significant discoveries and advancements. Here is an overview of key milestones:


Early Observations: 

Throughout history, various cultures recognized the importance of wound care and observed factors that influenced healing outcomes. Ancient Egyptians documented the use of natural substances like honey and resin as wound dressings. In ancient Greece, the physician Hippocrates emphasized cleanliness and prescribed herbal remedies for wound healing.


19th Century: 

The 19th century witnessed groundbreaking advancements in wound healing research. Louis Pasteur's germ theory demonstrated the role of microorganisms in wound infections, leading to the development of antiseptic techniques. Joseph Lister, a British surgeon, introduced carbolic acid (phenol) as an antiseptic, significantly reducing infections and improving healing outcomes.


20th Century: 

The 20th century brought significant progress in wound healing research. The discovery and development of antibiotics, starting with penicillin, provided an effective means to combat bacterial infections associated with wounds. This marked a major milestone in preventing wound complications and improving healing rates.


1950s-1970s: 

During this period, researchers began exploring different approaches to wound healing. Skin grafts, initially using the patient's own skin (autografts), were introduced for severe wounds. Later, allografts (skin from another human) and xenografts (skin from animals) became viable alternatives. Additionally, synthetic materials like hydrogels and polymers were developed as wound dressings, providing improved moisture management and protection.


Late 20th Century: 

The late 20th century saw significant advancements in understanding the molecular and cellular mechanisms of wound healing. Researchers discovered and studied growth factors, such as platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-β), which play vital roles in regulating various stages of the wound healing process. These discoveries opened up new avenues for targeted therapies and interventions.


1990s: 

The field of tissue engineering emerged as a promising approach for wound healing and tissue regeneration. Researchers began exploring the use of biomaterial scaffolds combined with cells and growth factors to create artificial skin substitutes and tissue-engineered constructs. This approach aimed to replace damaged tissues and promote functional regeneration.


2000s: 

Stem cell research gained traction in regenerative medicine and wound healing. Adult stem cells, especially mesenchymal stem cells (MSCs), were found to possess regenerative properties and the ability to modulate the wound microenvironment. MSCs showed promise in promoting tissue repair, reducing inflammation, and enhancing angiogenesis (formation of new blood vessels) at the wound site.


Present Day: 

Current research in wound healing and regenerative medicine focuses on a multidisciplinary approach. Scientists investigate the synergistic use of stem cells, growth factors, biomaterials, gene therapy, and tissue engineering techniques to optimize wound healing outcomes. This includes the development of advanced wound dressings, 3D-printed scaffolds, and biocompatible materials that mimic the extracellular matrix. Moreover, the integration of artificial intelligence, nanotechnology, and personalized medicine holds immense potential in tailoring treatments for individual patients.


The continuous advancements in wound healing research within regenerative medicine have significantly improved our understanding of the complex processes involved in tissue repair. With ongoing scientific endeavors, the field aims to address challenges such as chronic wounds, scar formation, and tissue regeneration, ultimately enhancing patient outcomes and quality of life.

Wound Healing

Here are some research papers.

Nazihah Bakhtyar; Exosomes from acellular Wharton's jelly of the human umbilical cord promotes skin wound healing; Stem Cell Res Ther. 2018 Jul 13;9(1):193.

Ryutaro Shohara; Mesenchymal stromal cells of human umbilical cord Wharton's jelly accelerate wound healing by paracrine mechanisms; Cytotherapy. 2012 Nov;14(10):1171-81.

Mehra Nazempour; The effect of allogenic human Wharton's jelly stem cells seeded onto acellular dermal matrix in healing of rat burn wounds; J Cosmet Dermatol. 2020 Apr;19(4):995-1001.

Caroline Mathen; Evaluation of Potential Application of Wharton's Jelly-Derived Human Mesenchymal Stromal Cells and its Conditioned Media for Dermal Regeneration using Rat Wound Healing Model; Cells Tissues Organs. 2021;210(1):31-44.

Meirong Li, Mesenchymal stem cell-conditioned medium accelerates wound healing with fewer scars, Int Wound J. 2017 Feb; 14(1): 64–73. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7949734/

Anitua, E., et al. (2015). Plasma rich in growth factors (PRGF-Endoret) stimulates proliferation and migration of primary keratinocytes and fibroblasts, and promotes reepithelialization and granulation tissue formation in an in vitro wound healing model. Journal of Biomedical Materials Research Part A, 103(3), 1011-1019.

Barrientos, S., et al. (2008). Growth factors and cytokines in wound healing. Wound Repair and Regeneration, 16(5), 585-601.

Gao, F., et al. (2016). Mesenchymal stem cells and immunomodulation: Current status and future prospects. Cell Death & Disease, 7(1), e2062.

Hou, J., et al. (2014). Conditioned medium derived from mesenchymal stem cells works synergistically with TNF-α to promote viability and migration of umbilical cord-derived mesenchymal stem cells and wound healing. Cell Transplantation, 23(7), 853-869.

Li, M., et al. (2012). Stem cell secretome: A promising candidate therapeutic tool for myocardial repair. Biomedical Reports, 1(6), 821-824.

Li, M., et al. (2016). Conditioned medium from adipose-derived stem cells efficiently promotes wound healing in genetically diabetic mice. Plastic and Reconstructive Surgery, 138(4), 846-859.

Roemeling-van Rhijn, M., et al. (2013). Inflammatory conditions affect gene expression and function of human adipose tissue-derived mesenchymal stem cells. Clinical & Experimental Immunology, 174(3), 469-481.

Sohni, A., et al. (2017). Mesenchymal stem cells prevent allostimulation in vivo and control checkpoints of Th1 priming: Migration of human DC to lymph nodes and NK cell activation. Stem Cells International, 2017, 6516854.

Wang, L., et al. (2017). Human adipose-derived mesenchymal stem cell-secreted CXCL1 and CXCL8 facilitate breast tumor growth by promoting angiogenesis. Stem Cells, 35(9), 2060-2070.

Wu, Y., et al. (2017). Conditioned medium from umbilical cord mesenchymal stem cells induces migration and angiogenesis. Molecular Medicine Reports, 16(1), 127-135.

Liu Y., et al. (2019) Stem Cell-Derived Exosomes in Wound Healing: Current Status and Prospects. Molecular Pharmaceutics, 16(1), 58-66.

Zhang Q., et al. (2017) Effects of human mesenchymal stem cell-derived conditioned media on skin wound healing. Journal of Tissue Engineering and Regenerative Medicine, 11(10), 2891-2903.

Yang Y., et al. (2017) Role of mesenchymal stem cells in bone regeneration and fracture repair: A review. International Orthopaedics, 41(12), 2619-2627.

Fu X., et al. (2019) Exosomes in burn injury and skin regeneration. Burns & Trauma, 7, 38.

Zhang Q., et al. (2015) Human gingiva-derived mesenchymal stem cells elicit polarization of M2 macrophages and enhance cutaneous wound healing. Stem Cells, 33(3), 526-537.

Stoff A., et al. (2018) Biologically active interleukin-6 as a biomarker in wound healing. Advances in Wound Care, 7(2), 57-62.

Reza A.M.M.T., et al. (2019) Curcumin: A potential candidate for matrix metalloproteinase inhibitors. Expert Opinion on Therapeutic Targets, 23(9), 1-17.

Shi R., et al. (2018) Stem cell therapy for organ fibrosis. Cell Transplantation, 27(6), 853-862.

Wu Y., et al. (2020) Extracellular vesicles in autoimmune diseases: Hope or hype? Frontiers in Immunology, 11, 965.

Caplan A.I. (2017) Mesenchymal stem cells: Time to change the name! Stem Cells Translational Medicine, 6(6), 1445-1451.

Lai R.C., et al. (2013) Exosome secretion: A novel cell function regulated by p53 and Rab27b/Rab27a pathways. Traffic, 13(3), 354-362.

Tsiapalis D., et al. (2018) Extracellular vesicles as a platform for tissue repair and regeneration. Journal of Controlled Release, 274, 24-37.

Wang M., et al. (2019) The role of extracellular vesicles in mediating progression, metastasis and potential treatment of hepatocellular carcinoma. Oncotarget, 10(26), 2453-2462.

Tonda-Turo C., et al. (2020) Current and future directions in wound healing: From cellular strategies to bioengineering approaches. Advanced Healthcare Materials, 9(17), 2000207.

Wang L., et al. (2020) Mesenchymal stem cell-derived exosomes: Roles in tumor growth, progression, and drug resistance. Stem Cells International, 2020, 8825771.

Marędziak M., et al. (2019) Stem cells as a way to improve wound healing. Medical Science Monitor, 25, 3949-3957.

Nawaz M., et al. (2018) Extracellular vesicles: Evolving factors in stem cell biology. Stem Cells International, 2018, 1742047.

Wang W., et al. (2019) Microvesicles and stem cells in corneal regeneration. Journal of Ophthalmology, 2019, 5258740.

Zhang B., et al. (2020) Advances in therapeutic applications of extracellular vesicles. Expert Opinion on Biological Therapy, 20(5), 533-546.

Khayambashi P., et al. (2020) Role of extracellular vesicles in cardiovascular repair and regeneration. European Journal of Pharmacology, 887, 173577.

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