**5. Discussion**

Botulinum toxin and fillers have been the standard introductory maintenance treatment for the improvement of age-related lines and volumetric lines for many years. "Filler fatigue" is a growing phenomenon, especially when the cost of treatment is calculated. As with any repeated procedure, the cost is not only monetary. For most patients, time spent recovering from a procedure, which limits their ability to work or enjoy leisure activities, is a real concern. Many tend to choose a lesser procedure based solely on "down" time. The lack of longevity with filler and toxin injections is a common complaint. As patients age, many note that the problem they are experiencing cannot be adequately addressed with these two types of injections. Regenerative options are being sought as an alternative to standard approaches, as restoration of one's own tissues is preferred to injecting toxins or foreign substances. Microlifting [20], a term coined by Tiryaki, is an approach that generally combines subcutaneous thread placement with other regenerative approaches.

While stem cell therapy is regarded as the highest form of regenerative medicine, recent research disputes that conventional wisdom. Many papers in different specialties note that cell-to-cell signaling has much more of an effect at the treatment target than the progenitor cells themselves do [21]. Exosomes are present in all tissues. They are formed when endosomes, or intracellular multivesicular particles, fuse with the cell's plasma membrane. Smaller nanoparticulate vesicles "bud out" into the intercellular space (**Figure 8**). Exosomes are able to communicate with other cells without making direct contact. In the early 1980s, exosomes were thought to be a receptacle for intracellular waste. Named in 1987, exosomes [22] were found to be the messengers that transfer behavior instructions to a recipient cell located in the region. The "paracrine effect" is the way that exosomes communicate with target cells (**Figure 7**). These nanoparticles generally measure 20–100 microns and less than 0.1 micron. They reside within endosomes, which are multivesicular organelles located within the cell. After binding with the internal plasma membrane, these nanoparticles are released outside the cell. Able to communicate with multiple cells in the region, exosomes are capable of inducing a change in behavior of a nearby cell without depending on direct cell contact.

**61**

**Figure 8.**

*cellular behavior in a distant location.*

*Combining PDO Threads with Exosomes for Microlifting DOI: http://dx.doi.org/10.5772/intechopen.91796*

They contain messenger RNA, microRNA, proteins, lipids, cytokines, bioactive compounds, and nucleic acids [23]. **Figure 9** shows the formation of exosomes from intracellular endosomes. Exosomes have been shown to promote proliferation of the target cell and more rapid healing than with a PBS buffer or depleted media in vitro [24]. Repair of injury with exosomes was noted to be three times as fast as the injury

*(A) Autrocrine signaling occurs when intracellularly derived particles influence the same cell at the* 

*extracellular membrane level. (B) Paracrine signaling occurs when exosomes are released into the extracellular fluid, thus influencing the behavior of cells within the local region. (C) Direct cell to cell communication can occur when adjacent cells build nanotunnels through which intracellular proteins and RNA is shared. (D) Endocrine signaling occurs when a substance such as a hormone enters the nearby bloodstream, influencing* 

*Cosmetic Surgery*

**5. Discussion**

*Diagram of intracellular exosomes.*

**Figure 7.**

Botulinum toxin and fillers have been the standard introductory maintenance treatment for the improvement of age-related lines and volumetric lines for many years. "Filler fatigue" is a growing phenomenon, especially when the cost of treatment is calculated. As with any repeated procedure, the cost is not only monetary. For most patients, time spent recovering from a procedure, which limits their ability to work or enjoy leisure activities, is a real concern. Many tend to choose a lesser procedure based solely on "down" time. The lack of longevity with filler and toxin injections is a common complaint. As patients age, many note that the problem they are experiencing cannot be adequately addressed with these two types of injections. Regenerative options are being sought as an alternative to standard approaches, as restoration of one's own tissues is preferred to injecting toxins or foreign substances. Microlifting [20], a term coined by Tiryaki, is an approach that generally combines

subcutaneous thread placement with other regenerative approaches.

While stem cell therapy is regarded as the highest form of regenerative medicine, recent research disputes that conventional wisdom. Many papers in different specialties note that cell-to-cell signaling has much more of an effect at the treatment target than the progenitor cells themselves do [21]. Exosomes are present in all tissues. They are formed when endosomes, or intracellular multivesicular particles, fuse with the cell's plasma membrane. Smaller nanoparticulate vesicles "bud out" into the intercellular space (**Figure 8**). Exosomes are able to communicate with other cells without making direct contact. In the early 1980s, exosomes were thought to be a receptacle for intracellular waste. Named in 1987, exosomes [22] were found to be the messengers that transfer behavior instructions to a recipient cell located in the region. The "paracrine effect" is the way that exosomes communicate with target cells (**Figure 7**). These nanoparticles generally measure 20–100 microns and less than 0.1 micron. They reside within endosomes, which are multivesicular organelles located within the cell. After binding with the internal plasma membrane, these nanoparticles are released outside the cell. Able to communicate with multiple cells in the region, exosomes are capable of inducing a change in behavior of a nearby cell without depending on direct cell contact.

**60**

They contain messenger RNA, microRNA, proteins, lipids, cytokines, bioactive compounds, and nucleic acids [23]. **Figure 9** shows the formation of exosomes from intracellular endosomes. Exosomes have been shown to promote proliferation of the target cell and more rapid healing than with a PBS buffer or depleted media in vitro [24]. Repair of injury with exosomes was noted to be three times as fast as the injury

#### **Figure 8.**

*(A) Autrocrine signaling occurs when intracellularly derived particles influence the same cell at the extracellular membrane level. (B) Paracrine signaling occurs when exosomes are released into the extracellular fluid, thus influencing the behavior of cells within the local region. (C) Direct cell to cell communication can occur when adjacent cells build nanotunnels through which intracellular proteins and RNA is shared. (D) Endocrine signaling occurs when a substance such as a hormone enters the nearby bloodstream, influencing cellular behavior in a distant location.*

#### **Figure 9.**

*Clinical effect of exosomes. (A) A 62-year-old patient 2 days following ablative erbium laser resurfacing. (B) The same patient on day 5. Usually these patients require 7–10 days of healing in order to achieve re-epithelialization.*

treated with buffer alone and two times as fast as the region treated with depleted media. The response was dose related; the dose of 10 mcg/ml seemed optimal in laboratory conditions. Clinical use of topical exosomes is noted to improve healing in patients who undergo fractional resurfacing procedures.
