Mechanisms by Which Stem Cell Therapy Might Treat Skin Aging

There is some interest in the research community in targeting first generation stem cell therapies to the skin in order to reverse skin aging. These stem cell therapies use cells obtained from fat tissue or other well established sources, and in near all cases the transplanted cells near all die quite quickly following their introduction into the patient. Methods of cell production and sources of cells vary widely, and so do the observed benefits. Increased regeneration is widely claimed, but only intermittently proven. Benefits realized by patients largely derive from reductions in systemic inflammation and other effects on cell behavior resulting from the signaling provided briefly by the transplanted stem cells.

Today's open access paper on stem cell therapy in the context of the treatment of photoaging in the skin is an interesting companion piece to a recent review and earlier report on the use of mesenchymal stem cells in aging skin. Treatment of skin aging is an field of medicine almost swamped by the nonsense put out by the "anti-aging" marketplace, but there is some evidence for treatment with stem cells to be helpful. Caveat emptor, of course.

The Paracrine Effect of Adipose-Derived Stem Cells Orchestrates Competition between Different Damaged Dermal Fibroblasts to Repair UVB-Induced Skin Aging

Human dermal fibroblasts (HDFs) are the primary cell type in the dermis and are responsible for extracellular matrix (ECM) deposition and remodeling, supplying skin with structural integrity and elasticity. In the process of skin aging, the quantity and proliferation rates of HDFs are declined, and collagen is reduced. On the other hand, matrix-degrading metalloproteinases (MMPs) are increased, degrading and changing the structure of the ECM, which accelerates the breakdown of connective tissue. All of these changes result in the thinning of the dermis, enhancement of wrinkles, and loss of elasticity.

Skin aging is caused by intrinsic factors (e.g., time, genetic factors, and hormones) and extrinsic factors (e.g., ultraviolet (UV) exposure and pollution). Eighty percent of skin aging primarily results from exposure to UV light, which is known as photoaging. Ultraviolet B (UVB) radiation penetrates the epithelial layer and causes DNA damage in the dermis of the skin. However, most UVB radiation directly affects cells in the upper dermis. Compared with HDFs in the lower dermis, more HDFs in the upper dermis suffer UVB-induced DNA damage. Failure of aged-cellular repair results in cell death. Healthy cells are gradually generated to replace the damaged cells to keep homeostasis.

Currently, some clinical studies have shown that autologous fat grafting, nanofat, and adipose stromal cells reduce wrinkles, increase dermal thickness, improve skin elasticity, and whiten skin. Adipose-derived stem cells (ASCs) play an important role in these therapies. ASCs have the ability to differentiate into different cell lineages, such as adipocytes, endothelial cells (ECs), osteocytes, cardiomyocytes, and neurons. In addition, ASCs secrete various biologically active molecules to repair damaged neighboring cells and influence the surrounding microenvironment. ASCs are considered a promising tool for cell-based therapy, especially in skin rejuvenation, wound healing, and scar remodeling. Because ASCs are usually injected into the subcutaneous fat layer, the paracrine effect of ASCs is the main mechanism by which skin rejuvenation occurs. However, the role of the paracrine effect of ASCs on the repair of different UVB-induced damaged HDFs is still unknown.

We hypothesized that ASCs could repair different UVB-damaged HDFs to various degrees via paracrine factors. To induce photoaging and natural aging in vitro and in vivo, HDFs and nude mice were irradiated with UVB light, and the control group received no irradiation. We found that ASCs enhanced HDF cell function. However, nonirradiated HDFs were more robust than UVB-irradiated HDFs after coculture with ASCs. This finding suggests that ASC treatment may more strongly impact HDFs in the lower dermis.


I'm all for prioritizing skin and hair aging, I can't think of a more efficient way to get the general public on board with rejuvenation therapies than starting with what they can see right before their eyes and appealing to their vanity.

Posted by: Corbin at May 21st, 2021 2:57 PM

It would probably be better if they could just get the adipose stem cells to differentiate into fresh fibroblasts which actually integrate into the skin.

I read about a modified version of CRISPR being used to act as artificial transcription factors to force them to differentiate into certain cell types.

Posted by: Jimofoz at May 22nd, 2021 6:58 PM
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