(courtesy of Carl C, our superman)
Tissue Engineering Advance: Implications For FtM Phalloplasty
SciMed – Hormones, Meds & Surgery
TS-Si News Service
Thursday, 07 May 2009 02:00
Linköping, Sweden. Scientists can now create cartilage, bones and the internal walls of blood vessels by using common connective tissue cells from human skin. Researchers in reconstructive plastic surgery at Linköping Universitet successfully manipulated these tissue cells to take on different shapes depending on the medium used for cultivation.
This is a practical example of an autologous biological process, where cells, tissues or even proteins can be reimplanted in the same individual who donated the materials in the first place. Candidate materials for autografts ordinarily include a variety of natural donor sites, including bone, bone marrow, cartilage, and skin biopsy.
There are obvious implications for generating new and improved techniques for Sex Reassignment Surgery (SRS), including phalloplasty, a continuing issue for F2M patients (cf. sidebar).
Phalloplasty is the construction or repair of a penis. In natal males, it can involve modification of an existing penis to correct the effects of an injury or to achieve cosmetic goals. Dr. Harold Gillies performed the first phalloplasty for FtM sex reassignment on Michael Dillon in 1946, a story documented in The First Man-Made Man by Pagan Kennedy.
In general, the sex organs of natal males and females evolve from the same human tissue. For instance, the glans penis is made of the same basic material as the clitoral glans (i.e., they are homologous). Likewise, the male corpora cavernosa are homologous to the clitoral body. Among other examples are the pairings of corpus spongiosum/vestibular bulbs (beneath the labia minora) and the foreskin/clitoral hood. The scrotum is homologous to the labia minora/majora.
Because of these homologous relationships, the combination of hormone therapy and surgical intervention offers opportunities for effective transformation. Over the long term, natural tissue replacement in the body (under hormonal supervision) enhances the outcome.
Basic surgical procedures are similar ro those used on natal males (except in extreme cases). The labia are united to form a scrotum capable of housing prosthetic testicles. However, the urethra must be lengthened since it ends near the vaginal opening, a source of many (if not most) surgical complications.
Sexual penetration is possible following the replacement of the erectile tissue with an erectile prosthesis. Ordinarily, this is done as a separate surgery to reduce risks and promote healing.
Historically, phalloplasty techniques included grafts from the arm, leg, abdomen or musculocutaneous latissimus dorsi, replanting abdominal muscle, or relocating fatty tissue from the abdomen.Another important technique has been the insertion of living bone (long-term follow-up studies in Germany and Turkey show that stiffness is maintained without late complications.
A more contemporary option is metoidioplasty involves enlarging the preexistent clitoris by hormone replacement therapy and fashioning a small penis that can be enlarged using other techniques.
Surgical techniques for FtM patients have advanced since the first phalloplasty, but much remains to be done. This situation is changing with new research efforts and the arrival of practical techniques derived from bioengineered tissue cultures.
Bone, cartilage and blood vessels are important components in reconstructive surgery, when damaged or missing tissue needs to be recreated. Minor fractures can heal spontaneously but for major bone damage and cartilage injuries there is the need to transplant tissue from other parts of the patient’s body.
The studies are the first in the world with results that show connective tissue cells from human skin transformed into other so called phenotypes and creating other types of tissue. Previously, researcher have attempted to grow autologous tissue from stem cells, such as those present in bone marrow. These cells, however, can be difficult to harvest, cultivate and store.
Connective tissue cells from human skin have great comparative advantages. A small biopsy is often sufficient to collect a useful number of cells.
Gunnar Kratz is a Professor of Experimental Plastic Surgery and team leader for the research group. “This means that it will be much easier to produce autologous tissue, which is tissue created from the patient’s own body”, he says. The results of the group’s research are now published in three simultaneous scientific articles. [C1-3]
According to Kratz, connective tissue cells “… are the `weed’ cells of the body, very easy to collect and cultivate into the cell type required. They are also very suitable to use to create a personal cell bank.”
Working with colleagues, Kratz has developed a technique to grow bone-like, cartilage-like and endothelial-like cells from connective tissue cells. Endothelial cells are the building blocks for the inner walls of blood vessels and line the entire circulatory system, reducing the turbulence of blood flow and allowing further pumping of blood fluids.
The new technique has been used to create whole tissue in gelatine scaffolds. Currently, preparations are underway to transplant these complete tissue pieces into laboratory animals.
In the their studies, the researchers collected connective tissue cells from healthy skin left over from breast and stomach plastic surgery and used fat stem cells to provide a comparison. To ensure that the transformation was not a result of the fusion of different cells, connective tissue cells from one cloned cell were also used.
The cell cultures were cultivated in four different environments optimised for
bone,
cartilage,
fat and
endothelium.
After two to four weeks the connective tissue cells had produced cartilage and bone mass to a greater extent than the fat stem cells had. The cells showed
several functions normally only present in the genuine (or conventionally ocurring) cell type.
capabilities as building material for three dimensional tissues, to create capillary networks, and other functions important to regenerative medicine.
“The dream is to be able to manipulate connective tissue cells in the human body to develop into specific cell types, for example to create bone cells for broken bones”, says Kratz. And much more.
Citation[C1] Engineering three-dimensional cartilage- and bone-like tissues using human dermal fibroblasts and macroporous gelatine microcarriers. Pehr Sommar, Sofia Pettersson, Charlotte Ness, Hans Johnson, Gunnar Kratz, Johan P.E. Junker. Journal of Plastic Reconstructive & Aesthetic Surgery. Feburary 2009. doi: 10.1016/j.bjps.2009.02.072
Summary
The creation of tissue-engineered cartilage and bone, using cells from an easily available source seeded on a suitable biomaterial, may have a vast impact on regenerative medicine. While various types of adult stem cells have shown promising results, their use is accompanied by difficulties associated with harvest and culture. The proposed inherent plasticity of dermally derived human fibroblasts may render them useful in tissue-engineering applications. In the present study, human dermal fibroblasts cultured on macroporous gelatine microcarriers encapsulated in platelet-rich plasma into three-dimensional constructs were differentiated towards chondrogenic and osteogenic phenotypes using specific induction media. The effect of flow-induced shear stress on osteogenic differentiation of fibroblasts was also evaluated. The generated tissue constructs were analysed after 4, 8 and 12 weeks using routine and immunohistochemical stainings as well as an enzyme activity assay. The chondrogenic-induced tissue constructs were composed of glycosaminoglycan-rich extracellular matrix, which stained positive for aggrecan. The osteogenic-induced tissue constructs were composed of mineralised extracellular matrix containing osteocalcin and osteonectin, with cells showing an increased alkaline phosphatase activity. Increased osteogenic differentiation was seen when applying flow-induced shear stress to the culture. Un-induced fibroblast controls did not form cartilage- or bone-like tissues. Our findings suggest that primary human dermal fibroblasts can be used to form cartilage- and bone-like tissues in vitro when cultured in specific induction media.
Keywords: Dermal fibroblast, Chondrogenesis, Osteogenesis, Microcarrier, Tissue engineering, Regenerative medicine.
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[C2] Adipogenic, chondrogenic and osteogenic differentiation of clonally derived human dermal fibroblasts. Johan P E Junker, Pehr Sommar, Mårten Skog, Hans Johnson, Gunnar Kratz. Cells, Tissues, Organs. In press.
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[C3] Human Dermal Fibroblasts: a Potential Cell Source for Endothelialization of Vascular Grafts. Lisa K Karlsson, Johan PE Junker, Magnus Grenegård, Gunnar Kratz. Annals of Vascular Surgery. Accepted.