Use of Stem Cell in Plastic Surgery

Outline

• Introduction

• Historical perspective

• Classification of stem cell

• Sources of stem cell

• Application of stem cells in plastic surgery

• Drawbacks

• Complications of stem cell in plastic surgery

• Future trends

• conclusion

Introduction

• The development of cell lines that may produce almost every tissue of the human body is an unprecedented scientific breakthrough. It is not too unrealistic to say that stem cell research has the potential to revolutionize the practice of medicine and improve the quality and length of life.

• Harold Varmus, Former Director, National Institutes of Health, and 1989 Nobel Laureate in Physiology or Medicine-December 2, 1998

• Stem cells are a unique population of undifferentiated biological cells that have the capacity to self-renew and differentiate into different cell types.

• This has revolutionized the therapeutic potential for regenerative medicine, tissue engineering, treatment of malignancy and the reconstructive prowess of plastic surgeons

• Stem cell therapy has provided effective treatment modalities for bony and soft tissue defects like traumatic skin defect and severe burn, non-healing wounds complicated by ischemia like diabetic foot.

Historical perspective

• “Stammzelle” (stem cell), was first used in 1868 in the work of the eminent German biologist Ernst Haeckel.

• Valentin Hacker in 1892 described “stem cells as the cells that later in development produce oocytes in the gonads.”

• In 1896 the Edmund Wilson(embryologist) reviewed these German scientists in his book ‘The Cell in Development and Inheritance.’

• Leroy Stevens, Bar Harbor, and Maine, 1960 from the Jackson Laboratory, discovered embryonal carcinoma cells while studying testicular carcinomas

•  early 1980s Gail Martins of the University of California - isolated stem cells from mouse.

•  In 1995, Jamie Thompson of the University of Wisconsin cultured monkey ESCs for the first time and subsequently human embryonic stem cells in 1999.

• Zuk et al, 2001 – adipose-derived stem cell

• Yin and Li, 2006 – stem cell niche ‘ as a specific site in adult tissue where stem cell reside and undergo self-renewal and produce large number of progeny’

• Yamanaka and Thompson, 2007 – induced pluripotent stem cells

• Yoshimura et al., 2008 - Breast augmentation and Facial lipoatrophy

Classification of stem cell

Based on the source of stem cell, the types include:

•  Embryonic stem cells (ESCs)

• isolated from the inner cell mass of pre-implantation embryos during the blastocyst stage

• pluripotent

• ethical concern

• tumourigenesis

• difficult to isolate

• Induced pluripotent stem (iPS) cells

• reprogramming of a somatic cell a pluriopotent stem cell.

• tumorigenesis

• Adult stem cells

• mesenchymal stem cell-bone marrow

• amniotic fluid and placental derived stem cells

• adipose tissue

• umbilical cord.

• epidermal

Adult stem cells

• Advantages -easily obtainable

• available in large quantities

• usually autologous

• no ethical concerns

• Disadvantages

• difficulty isolating one tissue

• limited phenotype

Degrees of potency

• Pluripotent stem cells: embryonic or induced pluripotent stem cells

• risks for teratoma formation

• ethical concerns

• Multipotent stem cells: mesenchymal stromal cells (MSCs)

• limited number of closely related cells

• Unipotent stem cells -can only produce one cell type-epidermal stem cells

Adipose-Derived Stem and Regenerative Cells

• prepared by digesting adipose tissue with collagenase

• expanding the adipocyte depleted fraction in tissue culture under standard conditions to create a homogenous population of adherent ADSCs

• The adipocyte-depleted nucleated cell population is commonly referred to as stromal vascular fraction (SVF)

SVF Isolation

• Enzymatic approach –gold standard

• nonenzymatic approaches -emulsifying agents

• ultrasonic energy

Cells contained in SVF

• Stroma cells (interstitial cells e.g fibroblasts, preadipocytes, and tissue macrophages)

• Vasculature (endothelial cells, vascular smooth muscle cells, and pericytes)

• blood-derived cells (CD45+),

• adipose-derived stem cells (ADSC)/fibroblast (CD31−CD34 + CD45−CD90+),

• endothelial (progenitor) cells (CD31 + CD34 + CD45−),

• pericytes(CD90 + CD146+)

Potential Regenerative Mechanisms of SVF

Angiogenesis

• vessel-forming cells-endothelial, smooth muscle, endothelial progenitor cells

• angiogenic growth factors including bFGF, PDGF, VEGF

Anti-apoptosis

• growth factor secretion

• direct cell-cell interaction

Potential Regenerative Mechanisms of SVF

• Anti-inflammation and Antiscar Formation

• decrease local inflammation

• reduce tissue damage caused by activated leukocytes.

• reduce leukocyte (CD3+) infiltration

• increase expression of anti-inflammatory factors--IL-10, prostaglandins, INF-gamma,

• reduce expression of proinflammatory cytokines --TNF-alpha, IL-6,

Vehicles for deploying stem cells

• Hydrogels

• Collagen gels -MSCs

• Matrigel-solubilized basement membrane

• Bone marrow-or cord blood-derived MSCs

• Bilayered skin substitutes/living skin equivalents

• epidermal and dermal component plus stem cells

Methods of application of the stem cells

• topical application

• local injection,

• intravenous or systemic injection

• dermal or carrier application

• Acellular matrices or scaffolds can be used

Scaffold

• Biological

• Fibrin

• Elastin

• Collagen
• Synthetic

• Polylacticacid

• Polyglycolicacid

• Polyethylene glycol derivatives (PEG)

• secrete numerous growth factors and cytokines

• increase macrophage recruitment, enhance granulation tissue

• Improve vascularization

• ADSCs have also shown to be useful in treating pathological wound healing such as aberrant scar formation

Diabetic ulcers

• Stem cell therapy can be single or multiple

• Depends on the size, depth, and type of defect

• Adequate debridement

• Scaffold; Allogeneic dermis or a collagen sponge

• Artificial dermis (Terudermis) containing a thin silicone membrane is placed over collagen sponge

• Artificial dermis is cell treated

• Thin silicone cover easily peels off after 10-14 days

• 2 weeks after the application -vascular in growth

• thin skin graft is applied.

• Ischaemic wounds

• chronic radiation ulcers

• Ischaemic wounds

• chronic radiation ulcers

• Burn wound management using stem cell

• Endometrial stem cells plus MSCs -improves the vascularity and significantly improve the outcomes of severely burned patients

• Stem cell increase cell homing, differentiation, mobilization and adhesion, eventually improving wound healing.

• In vitro new skin substitute

• Reduces post burn scaring

• Increase skin graft survival

• Autologous keratinocyte-fibrin epidermal cell spray –major burns.

SOFT TISSUE AUGMENTATION AND REGENERATION

• Cell-assisted lipotransfer (CAL)

• cosmetic breast augmentation

• Lumpectomy reconstruction

• facial augmentation during face-lift and facial

contouring surgeries

• Face-lift and facial contouring surgeries –ADSCs

• Facial lipoatrophy

• Skin Anti-Aging Therapies

• Treatment of depressed scars –ADSCs

• Filler for traumatic/iatrogenic soft tissue defects -ADSCs

BONY RECONSTRUCTION

• Craniofacial defects -BMSCs and ADSCs

• Calvarial defects;

• ADSCs combined with milled autologous cancellous bone and fibrin glue

• large calvarial defect-new bone formation with near-complete ossification in three months

Maxilla and mandible -Mesimaket al 2009

• ADSC and BMSC transplants.

• utilize a multistep procedure

• Stem cells are combined with bone morphogenetic protein [BMP]-2 and BMP-7

• re-implanted into the patient’s muscle tissue to allow for ectopic bone formation

• the titanium-enclosed ectopic bone is transplanted as a composite microvascular flap to fill the bony defect

1-stage procedure -Sandor et al, 2013

• Harvested ADSCs seeded on a scaffold of β-tricalcium phosphate and BMP-2

• This is placed in a moulded titanium mesh to fill a mandibular defect.

• Bone formation and remodelling noted ten months after transplant

CARTILAGE FORMATION

• Clinically, autologous BMSCs have been used to repair articular cartilage defects

• -surgically transplanting collagen-embedded BMSCs

• -intra-articular injections of BMSCs

• ear auricle defects

• ADSCs transplanted into hyaline cartilage defects in patellofemoral joints 

• Peripheral nerve regeneration-BMSCs, ADSCs

• promote nerve regeneration when differentiated into neuronal-like lineages

• neurotrophic factor elaboration

• . Nerve growth factor (NGF)

• . Glial-derived growth factor (GDNF)

• . Brain-derived growth factor (BDNF)

Drawbacks

• Ethical challenges -ESC

• Immuno compatibility

• permanently maintain the desired cell types following differentiation

• Unwanted vascularity

Complications

• Rejection

• Tumour formation

Future trends

• The use and development of microfabrication technology to create vascularized tissues and organs are still being investigated

• More work need to be done on controlling proliferation of stem cells after transplantation, and the appropriate integration of the transplanted cells into their surrounding environment

• Skin and its appendages following major burn

• Large scale, randomized trials.

Conclusion

• The recent clinical advances in stem cell therapies suggest a promising future for regenerative medical therapies in plastic surgery

• However more work need to be done to ascertain the long term effect of this treatment modality.

• There is a great need of expertise in this field in our sub region.

References

• Castro-Govea Y, De La Garza-Pineda O, Lara-Arias J, et al. Cell-assisted lipo transfer for the treatment of parry-romberg syndrome. Arch Plast Surg. 2012; 39: 659–62

• Kamakura T, Ito K. Autologous cell-enriched fat grafting for breast augmentation. Aesthetic Plast Surg. 2011; 35: 1022–30.

• Yoshimura K, Sato K, AoiN, et al. Cellassisted lipotransfer for cosmetic breast augmentation: supportive use of adipose derived stem/stromal cells. Aesthetic Plast Surg. 2008; 32: 48–55; discussion 6-7.

• Yoshimura K, Sato K, AoiN, et al. Cellassisted lipotransfer for facial lipoatrophy: efficacy of clinical use of adipose-derived stem cells. Dermatol Surg. 2008; 34: 1178–85.

• Yoshimura K, Sato K, AoiN, et al. Cellassisted lipotransfer for facial lipoatrophy: efficacy of clinical use of adipose-derived stem cells. Dermatol Surg. 2008; 34: 1178–85.

• Lendeckel S, Jodicke A, Christophis P, et al. Autologous stem cells (adipose) and fibrin glue used to treat widespread traumatic calvarialdefects: case report. J Cranio-Maxillo-Facial Surg. 2004; 32: 370–3.

• Mesimaki K, Lindroos B, Tornwall J, et al. Novel maxillary reconstruction with ectopic bone formation by GMP adipose stem cells. Int J Oral Maxillofac Surg. 2009; 38: 201–9.

• Sandor GK, TuovinenVJ, Wolff J, et al. Adipose stem cell tissue-engineered construct used to treat large anterior mandibular defect: a case report and review of the clinical application of good manufacturing practice-level adipose stem cells for bone regeneration. J Oral Maxillofac Surg. 2013; 71: 938–50.

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