17/08/18
The field of regenerative medicine continues to make substantial advancement in the therapeutic strategies addressing urologic diseases (congenital or acquired dysfunction of the urinary system e.g kidney stones) and other diseases.
Tissue Engineering borrows principles from the field of cell biology,material science,transplantation and engineering in an effort to repair or replace damaged tissue.
Tissue Engineering (TE) has evolved over the past four decades into an international area of science that is being investigated in virtually every country of the world.
Tissue engineering is the use of combination of cells,engineering and material science and suitable biochemical and physiochemical factors to improve or replace biological tissues.
PS- Autologous tissues are tissues gotten from same individual to which it would be re-implanted .
TE approaches can be classified into two categories
1. Acellular technique
2. Cellular technique
Accelular technique entails the use of accelular matrices as a scaffold for organ regeneration requiring the host organ to incorporate new tissue onto the scaffold with proper layering and orientation.
PS- Scaffolds are materials that have been engineered to cause desirable cellular interaction to contribute to the formation of new functional tissues for medical purposes.
Scaffolds can be harvested from autologous,allogenic or xenogenic tissues and then processed by chemical and mechanical means to remove cellular component for eventual implantation.
Common cellular techniques employs the use of donor cells which are processed before implantation. These cells can be directly infected to the host or expanded and processed in culture, seeded onto a support matrix or scaffold and then implanted into the recipient.
STEM CELLS
Stem cells are undifferentiated cells with the ability to divide into culture and give rise to different forms of specialized cells. They are defined by their ability to regenerate (self-renew) and different into varieties of cellular types.
Types of stem cells
There are basically three types of stem cells
1. Totipotent Stem Cells - These are cells derived from the zygote and have the greatest differentiation potential and are capable of forming cells of ectoderm, mesoderm, endoderm and gonadal ridge linage.
2. Pluripotent Stem Cells - They are embryonic stem cells and embryonic germ cells and are isolated from the inner cell mass of the blastocyst and primodal germ cell respectively and they give rise to three germ layers and cell of the gonadal ridge.
3. Multipotent Stem Cells - They are harvested from developing germ layers or their respective adult organ and are capable of self renewal and differentiation into organ specific cell types.
We'll be taking a look at some areas where stem and tissue engineering has been applied .
BLADDER:
High pressure neurogenic bladders as seen in
association with myelomeningocele or spinal cord injury may require bladder augmentation using intestinal segments to achieve adequate capacity and low pressure storage. Use of intestinal segments can lead to complications of urolithiasis,metabolic disturbances, excessive mucous production,and malignant disease. Much work has been done in creating tissue engineered bladder substitutes to potentially avoid the metabolic and neoplastic complications. A variety of regenerative medicine techniques to create bladder wall substitutes have been examined. Acellular substitutes from decellularized scaffolds have been obtained from a variety of tissue sources including xenogenic and allogeneic SIS and bladder. One study showed successful regeneration of mouse bladder by implanting decellularized bladder matrix scaffold impregnated with fibroblast growth factor. The most noteworthy study to date used tissue engineered bladder wall substitutes in seven patients with neurogenic bladder.Autologous urothelial and smooth muscle cells were obtained through open biopsy,expanded invitro and then seeded onto artificial matrices before implantation. Although the authors noted changes in technique over the course of the study, four patients showed improved compliance and increased capacity. This study demonstrated the feasibility of using engineered tissue substitutes for partial hollow organ replacement in humans obviating the need for intestinal substitution. A multi-institutional Food and Drug Administration approved Phase 2 clinical trial is currently underway.Stem cell research has also played a major role in developing bladder substitutes. With muscle invasive transitional cell
carcinoma or severe persistent hemorrhagic cystitis, where cystectomy and urinary diversion are indicated, tissue biopsy
for in vitro expansion may not be indicated, feasible, or of low yield. The use of stem cells as a primary nonimmunogenic tissue
source for seeding of decellularized scaffolds is being heavily
investigated. Successful directed differentiation of human embryoid body derived stem cells into bladder urothelium has been reported, using coculture of stem cells with bladder mesenchyme to provide the adequate stimulatory effects of mesenchymal inductive cofactors.Co-culture of these stem cells with mesenchymal tissue and subsequent seeding on decellularized xenogenic SIS has been described to successfully form composite grafts. Although the function of these grafts was not tested invivo, these studies demonstrate the feasibility of generating stem cell-derived bladder substitutes .
CELL PROGRAMMING
Though all somatic cells of the human body have the same genome structure, differences in
chromatin organization and expression pattern of genes lead to the formation of various
types of cells with different physiology, function and morphology. Therefore, one
could speculate that by changing chromatin structure and pattern of gene expression, all cells can be converted to other cell types. The first cell reprogramming report has been
presented in an earlier report in which fibroblast cells converted into myocyte through
the overexpression of MyoD gene. In a later study, the nucleus of the fibroblast cell has been
transferred to the enucleated oocytes which finally led to the birth of Dolly sheep. Yamanaka shed some light on the biology underlying cell differentiation and cell fate by converting the mouse fibroblast to iPS cells in his studyDz one year later, Yamanaka and Thompson reported the generation of human iPS cells from fibroblast cells.The possibility of directing lineage specific reprogramming of cells opens a window to a vast range of new possibilities in tissue engineering and regenerative medicines . Here- in, generation of iPS cell lines is an important issue in the way to derive pluripotent cells from somatic cells.Instability of the genome, high cost of culture, lack of an efficient protocol for differentiation as well as the presence of tumorigenic potential upon transplantation
are among the main reasons for the slow progress of it's clinical applications.
Written by: Ndukwe Esther, a student of Genetics and Biotechnology in the University of Calabar, Nigeria.
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