Adipose Derived Stem cells in plastic surgery - Comment
Applications of adipose derived stem cells in plastic surgery.
Full presentation slides:
1. Stem Cells in Plastic Surgery Ahmed Atef Mohamed, Msc, MRCS Plastic Surgeon Mataria Teaching Hospital
2. • Stem cells are undifferentiated cells that have the capacity to self-renew and differentiate into multiple cell lines; they are divided into two main groups: Embryonic stem cells and Adult stem cells
3. • Yamanaka and Thomson in 2007 introduced a new class of stem cells called induced pluripotent stem (iPS) cells) which are derived by the genetic reprogramming of terminally differentiated multipotent stem cells into pluripotent stem cells.
4. • ESCs are pluripotent cells that can differentiate into any of the three primary germ layers. However, there are ethical concerns regarding the isolation of cells from live embryos. As a result, researchers have redirected attention to the adult stem cell populations as an alternative source
5. • Adult stem cells are multipotent cells that can differentiate into a limited number of cell types originating from the same germ layer. They have been identified in many tissues as the hematopoietic stem cells, mesenchymal, neural, intestinal, epidermal, hepatic and circulating endothelial progenitor cells.
6. • Adult stem cells are immuocompatible, with no ethical concerns, their use offers the advantage of Avoiding the issue of tumorigenicity and Costly reprogramming linked to the use of induced pluripotent stem cells.
7. Yin & Li in 2006, first described The stem cell niche as a specific site in adult tissues where stem cells reside and undergo self-renewal and produce large numbers of progeny.
8. • Niches are highly specialized for each type of stem cell, with a defined anatomical localization, and they are composed of -Stem cells -Supportive stromal cells (which interact with each other through cell surface receptors and soluble factors), together with the extracellular matrix (ECM) in which they are located. -Blood vessels carry systemic signals and provide a conduit for the recruitment of inflammatory and other circulating cells into the niche.
9. • It is a dynamic, specialized microenvironment, that regulates the balance between cellular self-renewal and differentiation. • The stem cell would become depleted if cell differentiation overwhelmed self-renewal. Similarly, unchecked stem cell self renewal would expand the stem cell population risking tumor.
10. • Stem cells remain undifferentiated until initiated in response to a signal derived from the niche. • Some cells proliferate to produce precursor cells to maintain the stem cell pool, while others divide to generate and differentiate into tissue specific cells. • These cells are responsible for regenerating and replenishing cells after trauma or disease and maintain tissue homeostasis throughout the life.
11. • Adult mesenchymal stem cells are multipotent cells that are capable of differentiating into mesenchymal lineages such as bone, cartilage, muscle, and fat. Bone marrow, Dental pulp and Adipose tissue
12. • A set of standards were proposed by the Mesenchymal and Tissue Stem Cell Committee of the International Society for Cellular Therapy to define human mesenchymal stem cells. (Dominici et al., 2006). – First, cells must be plastic adherent when maintained in standard culture conditions. – Second, they express specific surface antigens. – Third, the cells are capable of differentiation into osteoblasts, adipocytes and chondroblasts in vitro
13. • Adipose tissue represents an attractive source of adult stem cells, the interest in using Adipose-derived stem cells has rapidly grown especially among plastic surgeons. The isolation of adipose tissue is much easier than bone marrow, with less donor site morbidity and available in greater quantities
14. Adipose derived stem cells were first described in 2001 by Zuk et al.
15. Isolation of ASCs Isolation of ASCs
16. Isolation of ASCs
17. Culture of ASCs
18. Culture of ASCs
19. Confluent stage
20. Current Applications Of ASCs In Plastic Surgery
21. ASCs for clinical use ??? FDA Regulation CFR 21 part 1271.10 directly demonstrates that enzymatically isolated adipose stem cells derived from SVF for reconstructive purposes as beyond the scope of ‘minimal manipulation’ and therefore, a drug. Thus, any surgeon who wishes to use ASCs isolated via collagenase to submit an Investigational New Drug application to the FDA and have an approved Institutional Review Board with the referring Institution. U.S. Food and Drug Administration. CFR Code of Federal Regulations Title 21. Part 1271: Human cells, tissues and cellular and tissue- based products. (HCT/P) http://www.ecfr.gov/cgi-bin/text-idx?SID=8012a6e1e3b4f2df434a32ac73771376&mc=true&node=se21.8.1271_110&rgn=div8.
22. • Wound Healing • Soft Tissue Reconstruction • Cartilage Reconstruction • Bone Reconstruction • Peripheral Nerve Regeneration • Skin Rejuvenation Therapeutic effects of ASCs are attributed to two distinct mechanisms; paracrine pathway and cell differentiation.
23. Wound healing • ASCs integrate themselves with the local environment, contributing to wound healing by secreting growth factors, improving vascularization, differentiating into the required cells whether endothelial cells or keratinocytes.
24. • The autologous transplantation of ASCs has been shown to increase the survival of full-thickness skin grafts and promote wound healing (Zografou et al., 2011), and reduce post burn scaring (Klinger et al., 2008). • Rather than direct injection into the wound as done in the previous studies, ASCs could also be employed in tissue engineering for the production of new skin substitutes in vitro. Combination of autologous ASCs with type I collagen sponge matrix Wound healing
25. Soft Tissue Reconstruction • The regenerative potential of ASCs has been demonstrated with fat grafting for replacement of soft tissue. The autologous tissue utilized in fat grafting contains a variety of cells, including ASCs, which support tissue neovascularization and regeneration through secretion of angiogenic growth factors; and differentiation to adipocytes and vascular endothelial cells.
26. • Cell-assisted lipotransfer (CAL), a technique first described by Matsumoto et al. in 2006, combines aspirated fat with concentrated ASCs to create stem cell-rich fat grafts. This approach allows for marked improvements in the survival rate of transplanted fat with less fat resorption. • In 2008, Yoshimura et al. used CAL for cosmetic breast augmentation in forty patients with reported favourable aesthetic outcome. Soft Tissue Reconstruction
27. Breast Cancer concerns !!!!! • While there is little evidence with regard to CAL therapy for breast augmentation post-mastectomy, the American Society of Plastic Surgeons in 2012 has come to the conclusion that fat grafting does not increase the risk of breast cancer recurrence. It appears that ASCs may enhance the growth of active cells without affecting dormant cells, but because there is a need for more research in this setting. • The current recommendations are such that CAL therapy should be delayed for reconstructive purposes in breast cancer treatment until there is no evidence of active disease for a period of 7 years.
28. • CAL has also been used for facial lipoatrophy (Castro-Govea et al., 2012) as well as for facial augmentation during face-lift and facial contouring surgeries (Lee et al., 2012), with similar noted subjective clinical improvements. Soft Tissue Reconstruction
29. Bone reconstruction • ASCs by definition, are able to differentiate into osteoblasts, therefore they have been explored for bone regeneration therapies and have demonstrated promising results for craniofacial defects. • ASCs either combined with autologous cancellous bone or seeded in scaffold are capable of forming new bone and repairing calvarial defects in human cases. • ASCs are capable of ossifying bony defects and providing a non-invasive method of bony reconstruction without the associated donor site morbidity of traditional bone grafts
30. Future • The recent clinical advances in stem cell therapies suggest a promising future for regenerative medical therapies in plastic surgery. However, as the basic science of stem cell behavior continues to be revealed, cautious and controlled implementation of cell-based therapies will be crucial for the appropriate translation of this new technology to the clinical setting.
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