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2 Stem Cell Facial Rejuvenation Combination Therapies

Facial aging, a relentless march of time etched upon our skin, presents not just aesthetic concerns but also impacts our well-being. This intricate process unfolds due to a complex interplay between internal (intrinsic) factors like genetics and external (extrinsic) aggressors, primarily ultraviolet (UV) radiation. The consequences are a tapestry of visible changes – uneven pigmentation, wrinkle formation, a parched texture, thinning, and a loss of elasticity – robbing our skin of its youthful vibrancy.

1. Human Adipose Tissue Stem Cell-derived Exosomes + Fractional CO2 Laser for Acne Scars

In the pursuit of combating these age-related woes, regenerative medicine offers a glimmer of hope. Recent studies have explored the potential of stem cell therapies, particularly those utilizing mesenchymal stem cells (MSCs) derived from fat tissue (adipose-derived stem cells, ADSCs) to combat skin aging. These remarkable cells possess the ability to self-renew and transform into various cell types, making them prime candidates for rejuvenation. ADSCs, readily available and abundant, offer significant advantages over other stem cell sources. Studies, both in vivo (living organisms) and in vitro (laboratory settings), have demonstrated their efficacy in reversing the signs of aging in the skin. However, their widespread clinical application faces hurdles. Rare instances of tumor formation, low engraftment rates (successful establishment of transplanted cells), and challenges in quality control remain concerns.

Exosomes, nature's ingenious messengers, have emerged as a novel therapeutic strategy. These tiny, spherical extracellular vesicles, cloaked in a lipid bilayer and measuring a mere 30-200 nanometers, play a crucial role in cellular communication. MSCs secrete exosomes, which shuttle proteins and genetic material between cells, orchestrating a symphony of cellular responses. Intriguingly, MSC-derived exosomes seem to retain the therapeutic properties of their parent cells, offering a cell-free alternative to whole-cell therapy with MSCs. Furthermore, recent research suggests that the regenerative effects of ADSCs are mediated by their exosomes, aptly named Human Adipose Tissue Stem Cell-derived Exosomes (HAT-Exos). These HAT-Exos are gaining traction as safe, effective, and readily available therapeutic agents, circumventing the limitations associated with stem cell therapy.

Building upon the established anti-aging potential of ADSCs and the fascinating world of exosomes, few studies delve into the effectiveness of HAT-Exos. Few studies hypotize that HAT-Exos, delivered via a minimally invasive microneedling technique, can offer a safe and efficacious approach to combat facial skin aging. Through a randomized, split-face clinical trial, a study evaluate the impact of a human solution containing HAT-Exos (HATS) on wrinkles, skin elasticity, hydration, and pigmentation.

Current Treatment

Fractional CO2 laser (FCL) resurfacing remains the mainstay for treating atrophic acne scars due to its ability to induce controlled ablative fractional injury. This controlled injury triggers a robust neocollagenesis cascade, leading to scar remodeling and improvement in scar depth. However, FCL therapy presents a unique therapeutic challenge, balancing efficacy with a side-effect profile that can significantly impact patient experience and outcomes.

FCL technology utilizes a carbon dioxide laser to create microscopic zones of thermal injury within the epidermis and upper dermis. This controlled ablation initiates a wound healing response, characterized by an influx of inflammatory mediators and fibroblasts. The subsequent activation of fibroblasts stimulates the synthesis of new collagen, glycosaminoglycans, and elastin, leading to scar remodeling and a smoother surface topography. The fractional nature of the treatment allows for targeting of scar tissue while preserving surrounding healthy tissue, promoting faster re-epithelialization and minimizing downtime.

Despite its advantages, FCL resurfacing is not without limitations. The ablative nature of the treatment can lead to post-inflammatory hyperpigmentation (PIH), particularly in patients with Fitzpatrick skin types IV-VI. Careful preoperative assessment and optimization of post-procedural skincare regimens are crucial to minimize this risk. Additionally, thermal injury can induce dyspigmentation, manifesting as hypopigmentation, particularly in deeper zones of ablation. This necessitates meticulous control of laser parameters and a thorough understanding of individual patient skin characteristics.

Furthermore, the success of FCL resurfacing hinges on achieving a balance between optimal depth of ablation for effective scar remodeling and minimizing the risk of thermal damage and subsequent scarring. Deeper ablation offers superior scar improvement but increases the potential for adverse effects. Conversely, a more conservative approach may lead to suboptimal outcomes.

Mechanism of Action

ASCE therapy promotes wound healing and scar remodeling following fractional CO2 laser (FCL) resurfacing transcends the mere delivery of growth factors. While ASCEs undoubtedly possess a rich cargo of bioactive molecules, including growth factors, cytokines, and extracellular matrix components, their action is likely a more intricate orchestration at the cellular level.

Paracrine Modulation of Fibroblasts

ASCE-derived growth factors and signaling molecules are hypothesized to create a favorable microenvironment within the wounded dermis, specifically targeting fibroblasts, the principal orchestrators of scar formation. These factors may:

  • Stimulate Collagen Synthesis: ASCEs may promote the production of high-quality, Type I collagen by fibroblasts, leading to improved scar filling and a more aesthetically pleasing scar appearance.

  • Modulate Fibroblast Phenotype: The profibrotic to antifibrotic shift is crucial for scar remodeling. ASCE signaling may nudge fibroblasts towards a more reparative phenotype, promoting scar remodeling and deposition of well-organized extracellular matrix.

Anti-inflammatory and Immunomodulatory Effects

The post-FCL inflammatory response, while a necessary part of healing, can contribute to hyperpigmentation. ASCEs possess immunomodulatory properties. They may:

  • Downregulate Pro-inflammatory Cytokines: By mitigating excessive inflammation, ASCEs can potentially minimize the risk of post-inflammatory hyperpigmentation, a significant drawback of FCL therapy.

  • Promote Angiogenesis: Adequate vascularization is essential for optimal tissue healing. ASCEs may stimulate the formation of new blood vessels, ensuring proper nutrient delivery and facilitating the removal of cellular debris.

  • Enhanced Re-epithelialization: Keratinocyte proliferation and migration are crucial for wound closure. ASCE-derived factors may accelerate re-epithelialization, minimizing the risk of infection and promoting faster recovery times.

In essence, ASCEs may act as potent biological modulators, creating a microenvironment conducive to scar remodeling and improved healing. They likely go beyond simple growth factor delivery, influencing fibroblast behavior, modulating inflammation, and potentially promoting revascularization. This multifaceted approach holds promise for optimizing the therapeutic benefits of FCL resurfacing while mitigating its potential side effects.

2. Stem Cells Therapy + Microneedling

A study explores the potential of combining amniotic fluid-derived mesenchymal stem cell conditioned media (AF-MSC-CM) with microneedling for enhanced facial rejuvenation. While microneedling has established itself as a minimally invasive approach, this study delves into the possibility of augmenting its effects through the introduction of a rich source of growth factors.

The study demonstrates a statistically significant difference in facial rejuvenation between patients receiving the combined AF-MSC-CM and microneedling treatment compared to those receiving microneedling alone. This suggests a potential synergistic effect, where the growth factors in AF-MSC-CM act in concert with the micro-injuries induced by microneedling to promote a more robust regenerative response. Histological analysis revealed a notable increase in collagen and elastin fiber formation, particularly on the side treated with the combination therapy. This finding aligns with the proposed mechanism, where growth factors like TGF-β and IGF-1, known to be abundant in AF-MSC-CM, stimulate fibroblast activity and extracellular matrix synthesis. The observed improvement in fiber organization suggests a potential for superior structural support and elasticity within the dermis.

Current Treatment

Microneedling, a minimally invasive procedure, exerts its effects through a well-defined cascade. Microneedles create microscopic channels in the stratum corneum and upper dermis. This controlled injury triggers an inflammatory response, initiating the wound healing process. Keratinocytes and immune cells release pro-inflammatory cytokines and chemokines, such as IL-1α, IL-6, and TNF-α. These act as signaling molecules, recruiting fibroblasts and other inflammatory cells to the site of injury. The recruited fibroblasts become activated, upregulating the expression of growth factors like TGF-β and PDGF. These growth factors further stimulate collagen and elastin synthesis, leading to dermal thickening and improved skin texture. The inflammatory response also promotes the formation of new blood vessels (angiogenesis), enhancing nutrient and oxygen supply to the wounded area, thereby facilitating the healing process.

New Approach with Stem Cell

AF-MSC-CM, a cell-free supernatant derived from amniotic fluid mesenchymal stem cells, harbors a rich cocktail of growth factors, cytokines, and extracellular matrix (ECM) components. These biomolecules play a critical role in promoting tissue regeneration. AF-MSC-CM is enriched with growth factors like TGF-β, IGF-1, PDGF, VEGF, and FGF. These factors directly stimulate fibroblasts, promoting their proliferation and collagen and elastin synthesis. Additionally, they can enhance angiogenesis, further supporting tissue repair. AF-MSC-CM contains immunomodulatory factors like IL-10 and Prostaglandin E2, which mitigate excessive inflammation and promote tissue repair. This can be particularly beneficial in minimizing post-procedural side effects associated with microneedling. AF-MSC-CM is rich in ECM components like hyaluronic acid and proteoglycans. These molecules contribute to dermal hydration, improved skin elasticity, and provide a scaffold for cellular adhesion and migration.

The combination of microneedling and AF-MSC-CM creates a synergistic effect, potentially leading to superior facial rejuvenation outcomes. Microneedling creates temporary channels in the stratum corneum, facilitating the deeper penetration of growth factors present in AF-MSC-CM, maximizing their effect on dermal fibroblasts. The combination leverages the strengths of both modalities. Microneedling triggers the initial inflammatory cascade and fibroblast activation, while AF-MSC-CM provides a concentrated source of growth factors that further amplify collagen and elastin synthesis, leading to more robust tissue remodeling.

The immunomodulatory and ECM-remodeling properties of AF-MSC-CM contribute to the formation of well-organized collagen and elastin fibers, leading to improved skin texture and elasticity.

In conclusion, stem cell therapies, notably adipose-derived stem cells (ADSCs) and their exosome derivatives (HAT-Exos), offer promising avenues for rejuvenation, navigating past hurdles like tumor formation to herald a cell-free era of regenerative medicine. When coupled with innovative techniques like microneedling and the infusion of growth factor-rich amniotic fluid-derived mesenchymal stem cell conditioned media (AF-MSC-CM), these approaches form synergistic alliances, amplifying the regenerative cascade to restore collagen, elastin, and skin texture, promising a brighter horizon in the battle against facial aging.


Facial rejuvenation using stem cell conditioned media combined with skin needling: A split-face comparative study (2020)

Combination Treatment with Human Adipose Tissue Stem Cell-derived Exosomes and Fractional CO2 Laser for Acne Scars: A 12-week Prospective, Double-blind, Randomized, Split-face Study (2020)

Efficacy of combined treatment with human adipose tissue stem cell-derived exosome-containing solution and microneedling for facial skin aging: A 12-week prospective, randomized, split-face study (2023)

The investigation of the efficacy and safety of stromal vascular fraction in the treatment of nanofat-treated acne scar: a randomized blinded controlled clinical trial (2022)

Fractional CO2 Laser (2018)


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