Tag Archives: biology

Safety and Efficacy: Adipose Mesenchymal Stem Cell (ADSC) Secretome Is Superior to Bone Marrow Mesenchymal Stem Cell (BMSC) and Umbilical Cord Mesenchymal Stem Cell (UCSC) Secretomes

I list here some of the reasons why I formulate my skin care products using the secretome of adipose mesenchymal stem cells (ADSCs) instead of bone marrow mesenchymal stem cells or umbilical cord mesenchymal stem cells. ADSCs are better at reducing inflammation and setting the innate and adaptive immune systems into a pro-regenerative state, inducing collagen formation, and laying down that collagen in a manner that is anti-fibrotic. This is a small excerpt of my upcomming peer-reviewed publication.

Listing Efficacy of ADSCs Versus BMSCs versus UCMSCs Secretome (Exosomes + Soluble Fraction)

Bone Marrow Mesenchymal Stem Cells (BMSCs), and the molecules they release, prolong and enhance inflammation by increasing survival and function of neutrophils (Casatella et al, 2011; Liang et al, 2024). BMSC secretome also reprograms hematopoietic stem cells to become inflammatory white blood cells (Ng et al, 2023). Under hypoxic conditions, which induces the activation of TRL4, BMSCs secrete pro-inflammatory factors and decrease the polarization of macrophages from the M1 to M2 phenotype, the M2 type being anti-inflammatory and therefore the BMSCs are promoting more inflammation (Faulknor et al, 2017; Waterman et al, 2010). Thus, BMSCs cultured in normal hypoxic conditions in the laboratory are secreting pro-inflammatory factors and when administered to wounded skin will induce inflammation by recruiting neutrophils and M1 type pro-inflammatory macrophages.
ADSCs have consistently exhibited much greater anti‑inflammatory capabilities, phagocytic activity, anti‑apoptotic capability activity and cell viability over BMSCs (Li et al, 2019).
ADSCs have been found to be highly immunomodulating cells, exceeding the suppressive effect of BMSCs by secreting more anti-inflammatory IL-6 and transforming growth factor-β1 (TGF-β1) Ceccarelli et al (2020).
When compared with the BMSCs- and UCSCs-treated groups, the ADSCs-treated group exhibited markedly accelerated healing efficiency, characterized by increased wound closure rates, enhanced angiogenesis, and collagen deposition at the wound site in an animal model (Cao et al, 2024).
ADSCs have biological advantages over BMSCs in the proliferative capacity, secreted proteins (basic fibroblast growth factor, interferon-γ, and insulin-like growth factor-1), and immunomodulatory, ant-inflammatory effects (Li et al, 2015).
Differences in cytokine secretion cause ADSCs to have more potent immunomodulatory effects than BMSCs (Melief et al, 2013)
ADSCs are better at preventing fibrosis than BMSCs (Yoshida et al, 2023).
Adipose mesenchymal stem cell secretome is superior to that of BMSCs because it preferentially helps to rebuild the epidermis by stimulating basal keratinocytes (Ademi et al, 2023).
BMSCs express much CTHRC1 protein (Turlo et al, 2023), which may help to promote fibrosis (Liu et al, 2023).
ADSC exosomes contain SIRT1 (Huang et al, 2020) and activate SIRT1 in other cells (Liu et al, 2021) to reduce inflammation, improve mitochondrial function, and reduce senescence.
ADSC exosomes reduce inflammation in endothelial cells (Heo and Kim, 2022).
ADSCs are considered more powerful suppressors of immune response than mesenchymal stem cells (MSCs) derived from different tissue sources, including trabecular bone, bone marrow, dental pulp, and umbilical cord (Ribeiro et al., 2013; Nancarrow-Lei et al., 2017).
 ADSCs immunomodulatory effects exceed that of BMSCs (Melief et al., 2013).
ADSCs secrete higher amount of immune suppressive cytokines, such as IL-6 and transforming growth factor-β1 (TGF-β1) than do BMSCs (Soleymaninejadian et al., 2012; Melief et al., 2013; Montespan et al., 2014).
Bochev et al (2008) showed that ADSCs had a stronger ability to inhibit immunoglobulin (Ig) production by B cells than BMSCs.
Ivanova-Todorova E et al (2009) found that Adipose tissue-derived mesenchymal stem cells are more potent suppressors of the adaptive immune response through limiting dendritic cells differentiation compared to bone marrow-derived mesenchymal stem cells.
ADSC secretome inhibits LPS-induced proinflammatory cytokines (Li et al, 2018)
Human ADSCs are key regulators of immune tolerance, with the capacity to suppress T cell and inflammatory responses and to induce the generation/activation of antigen-specific regulatory T cells (Gonzalez-Rey et al, 2010).
ADSC secretome can suppress the activation, proliferation, and function of CD8+ T cells, which are inflammatory killer T cells (Kuca-Warnawin et al, 2020).
ADSC secretome was able to elevate expression of M2 macrophages and modified their cytokine expression to an anti-inflammatory profile (Hu et al, 2016; Zomer et al, 2020)
Exosomes secreted by human adipose mesenchymal stem cells promote scarless cutaneous repair by regulating extracellular matrix remodeling (Wang et al, 2017).
ADSC exosomes reduce inflammation and alleviate keloids by promoting mitochondrial autophagy through the PI3K/AKT/mTOR pathway (Liu et al, 2024).
ADSC exosomes reduce injury through the transfer of mitochondria components to neighboring cells (Xia et al, 2022).
ADSC secretome expedited wound healing and reduced inflammation in an animal model (Ma et al, 2021).
ADSC secretome promotes wound healing without leaving visible scars and was found safe when injected (An et al, 2021).
ADSC secretome has positive effects on granulation tissue formation and vascularization, and helps prevent fibrosis in pressure ulcers (Alexandrushkina et al, 2020).
Human ADSCs secrete functional neprilysin-bound exosomes that can degrade β-amyloid peptide (Aβ) that is found in the skin – cutaneous amyloidosis (Katsuda et al, 2013; Kucheryavykh et al, 2018).
In psoriasis and eczema the secretome from adipose mesenchymal stem cells (ADSCs), can regulate SOCS (suppressor of cytokine signaling) pathways, and modulate JAK pathways to reduce inflammation (Wang et al, 2022; Ko et al, 2023). Further, the secretome from ADSCs increases SOCS3 expression and, thus, the persistent and uninhibited expression of STAT3 by increased SOCS3 effectively ameliorates tissue injury by promoting tissue regeneration and decreasing inflammation and apoptosis (Lee et al, 2016).
ADSC and BMSC secretomes were characterized by the upregulation of proteins linked to ECM structure and organization and proteolytic processes compared to UCSCs, important to active involvement in tissue repair and microenvironment maintenance and suggesting their advantage for tissue-forming applications (Hodgson-Garms et al, 2025), but ADSCs are better at preventing fibrosis and reducing inflammation (Yoshida et al, 2023).
Fu et al (2025) found that hADSC-Exos are more effective in promoting hair follicle development compared to hUCMSC-Exos, and the secretome of ADSCs was more associated with growth processes such as nucleosome function than was the UCMSC secretome (Fu et al, 2025).

DNA Damage Repair: Animals Do It Better Than Plants and Microorganisms

Although plants and microorganisms such as algae possess some of the DNA damage response factors that are present in animal systems, they are missing many of the important regulators, such as the p53 tumor suppressor. The p53 mechanism halts the cell cycle when DNA damage is detected, giving repair machineries time to act. These observations point to the differences in the DNA damage response mechanisms between plants and animals. While DNA repair enzymes from plants may help the skin when topically applied, optimizing the DNA repair mechanisms inherent in animals is the optimal strategy for repairing DNA in animals. Adipose mesenchymal stem cell released molecules (secretome) help to optimize inherent DNA repair mechanisms when topically applied to the skin, including heat shock proteins. More importantly, the molecules help to rebuild the architecture of the skin, which prevents mutations from forming cancerous cells (see my Blog on this topic).

All plant extract contain DNA repair enzymes

If you’re using a product with plant extract, you’re likely using DNA repair enzymes. All, or nearly all, plants contain DNA repair enzymes. Keep in mind, this is important, an intrinsic feature of plant and microorganism DNA repair pathways is that they are not error-free, leading to potentially transmissible mutational alterations. The error-prone nature of some DNA repair mechanisms, however, increases the genetic diversity and variability of the populations, thus contributing to the evolution of plant genomes. In other words, despite the recent hype about DNA repair enzymes in plants/microorganisms, they don’t work well and are “error prone.”

Animals have more robust DNA reair enzymes than do plants

This is not true in animals. They are not error prone. Because animals must better protect their DNA than do plants to prevent and repair mutations that are harmeful, potentially lethal. This is why stem cells in the skin faciltate DNA repair as only animals can do.

Stem cells in the skin have the most robust DNA repair mechanisms

As stated in a presitigious scientific journal, Molecular Cell, ” adult stem cells are endowed with a superior capacity to prevent the accumulation of genetic lesions, repair them, or avoid their propagation to daughter cells, which would be particularly detrimental to the whole organism.” Further stated, “SCs [stem cells] count upon robust antioxidant defenses (which limit genotoxicity) and a superior DDR (to repair unavoidable damage). These mechanisms are in place to protect cellular homeostasis.” 

DNA repair mechanisms: it’s complicated and very efficient if enabled

DNA double strand breaks (DSBs) are a serious threat to genome stability and the erroneous repair of DNA may lead to chromosomal rearrangements with potentially lethal consequences, including cancer, for an organism. The response to DSBs elicits a highly complex and organized cellular program, called the DNA damage response (DDR), setting in motion processes that mitigate the adverse effects of DNA damage and facilitate DNA repair. Broken DNA is usually repaired by two mechanistically distinct pathways: homologous recombination (HR) and non-homologous end joining (NHEJ). HR is a complex, multistep process that allows large sections of DNA to move from one chromosome to another. NHEJ is a DNA repair mechanism that fuses broken DNA ends together without the need for a homologous template While HR uses a homologous DNA strand as a template for error-free repair, NHEJ is inherently error-prone and does not rely on sequence homology. The preferred mode of repair and cellular consequences of DDR varies between organisms and is also dependant on cell type and cell cycle context. For example, while HR is the preferred mode of repair in many unicellular organisms such as budding and fission yeast, NHEJ is the prevalent pathway in plants and animals.

Plants versus animals, digging deeper into the mechanisms

However, in many aspects, plants respond differently to DNA insults than do animals. The constant risk of tumor formation in animals has led to evolution of DDR that assures precise genome maintenance, often resulting in apoptotic death of significantly damaged cells. The lack of such a strong selective constraint presumably permitted evolution of a less potent DDR in plants, making plants more prone to genome damage. Furthermore, plant cells are exposed to high levels of genotoxic stress resulting from long-term exposure to solar ultraviolet (UV) irradiation, photosynthesis and extended periods of desiccation. Thus, some features of plant DDR and DSB repair may deviate from models primarily established from studies in yeasts and mammals.

DNA repair in animals is even more complicated than that described by the two major pathways. Five DNA repair mechanisms are usually distinguished: (a) direct DNA damage reversal, (b) BER, (c) mismatch repair (MMR), (d) nucleotide excision repair (NER), and (e) homologous recombination (HR) and non-homologous end joining (NHEJ). DNA repair pathways were originally restricted to the nuclear compartment. Ample evidence indicates that mitochondria possess a number of DNA repair factors and mechanisms shared with the nuclear processes.

From: Sottile and Nadin (2018). Sources of DNA damage and repair mechanisms. Endogenous and exogenous agents constantly impact on DNA. They may cause many different forms of DNA damage. The scheme shows the five major DNA repair mechanisms operating in the nucleus of mammalian cells capable of removing a wide range of DNA lesions: direct damage reversal, base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), homologous recombination (HR), and non-homologous end joining (NHEJ). The BER system may also be found in the mitochondria. ROS reactive oxygen species, IR ionizing radiation, TOPOII topoisomerase II

Not included in the above summary is a new form of DNA repair in animals, called neucleophagy. This was just reported in October 2024 by a group of scientists at Oxford. Found to be evolutionarily conserved and clinically relevant, we’ll know more baout this mechanism in the coming years. Its mediated by TEX264, an intrinsically disordered protein, and as such, I suspect this will be an important and widespread DNA repair mechanism, possibly involving adult stem cells and their secretome – stay tuned.

How adult adipose mesenchymal stem cell scretome faciltates DNA repair

These complicated processes are faciltated by a number of molecules, including proteins, such as heat shock proteins, released by adipose mesenchymal stem cells (ADSCs). Another example, ADSCs release sirtuins, which are involved in DNA repair. The sirtuins work both as protein activators and chromatin-structure-modifying enzymes. Deacetylation carried by sirtuins represents a basic epigenetic mechanism. Histone modifications including deacetylation and poly-(ADP)-ribosylation compromise an essential part of physiological ageing processes that are involved in the pathogenesis of ageing-related diseases. Stem cells are also known to produce 5-hydroxymethylcytosine binding, embryonic stem-cell-specific (HMCES) protein functions as an intermediate in DNA interstrand cross-link repair, part of BER. Antioxidants from ADSCs are also important for DNA repair. They include: Superoxide dismutase (SOD): This enzyme converts superoxide radicals (O2-) into hydrogen peroxide (H2O2), which is then further broken down by other enzymes like catalase. Catalase (CAT): Catalase directly breaks down hydrogen peroxide (H2O2) into water and oxygen, preventing further oxidative damage to cellular components including DNA.  Peroxiredoxins (Prxs): This family of enzymes also plays a significant role in scavenging reactive oxygen species, particularly in the nucleus where DNA is located, and can directly contribute to DNA repair mechanisms.

The secretome from ADSCs was tested for skin repair following irradiation, where DNA and protein damage is a key component in the radiation dermatitis. Working with Dr, Michael Traub, N.D., NeoGeneis found that simple topical application of ADSC secretome in its Recovery product significantly reduced radiation dermatitis. The Recovery works through the many types of molecules found in the ADSC (and fibroblast) secretome that enable the skin’s robust DNA repair mechanisms to work optimally.

Beyond the hype of plant/microorganism DNA repair enzymes

You can see that using the secretome from ADSCs is much more powerful than using a plant or microorganism extract to repair DNA. While DNA repair enzymes from plants and microorganisms have been found to reduce cyclobutane pyrimidine dimers, and presumably repair DNA in humans when compared to doing nothing, the “DNA repair” products on the market contain many other ingredients that are at least partially responsible for their efficacy. Those other ingredients include antioxidants and sunblocks. If you want a great topical product to repair DNA in your skin cells, use NeoGenesis Recovery that is full of the molecules released from ADSCs, including those molecules in exosomes and those molecules in the soluble fraction.