Tissue Engineering and Some Products of Tissue Engineering - Cell Therapy and Regenerative Medicine

Tissue Engineering

Tissue engineering, the multidisciplinary field of varied strategies to regenerate natural or grow new human tissues and organs, has burgeoned over the past 15 years (Mooney and Mikos, 1999; Brownlee, 2001; Petit-Zeman, 2001; Stock and Vacanti, 2001; Willis, 2004). Recently, a popular news magazine predicted that tissue engineering would be the hottest employment opportunity of the 21st century. Sometimes referred to as the more general term “regenerative medicine,” tissue engineering has in-tegrated biotechnology, clinical medicine, cell biology, developmental biology, and biomaterials engineering into an effort to overcome the challenges associated with conventional surgical approaches to tissue and organ repair or replacement. Each year, over eight million surgeries are performed in the U.S. alone torepair or replace human tissues and organs at staggering costs and significant patient discomfort (Vunjak-Novakovic, 2006). Only a fraction of patients admitted to the hospital in need of organs receive them due to the dearth of transplantable organs. Advances in biotechnology have created opportu-nities for the science of tissue engineering to address these challenges and improve health care. Another exciting application of tissue engineering is the delivery of biotechnology-produced drugs using engineered tissue materials as controlled-release and microfluidic drug delivery vehicles (Saltzman and Olbricht, 2002).

Some Products of Tissue Engineering

Regenerative medicine has had success in stimulating the body’s own repair mechanisms by mimicking the action of endogenous growth factors. For example, recombinant DNA technology has produced such drugs as epoetin alfa, filgrastim, and sargramostim that accomplish just that in the hematopoietic system. Research is underway to test new tissue growth factors for their ability to regenerate human tissue. Active research programs are studying the effect of growth factors on wound healing, bone repair, blood vessel generation, and nerve regenera-tion. Successes in genomics and proteomics should have a major impact on tissue engineering as new growth factor genes are discovered.

Several products of tissue engineering are now available for use as replacement skin and cartilage. The leading skin product is graftskin (Apligraf), approved by the FDA in 1998. It is a living skin equivalent indicated for the treatment of foot and leg ulcers. Generated in tissue culture and started from cells of human foreskin removed during infants’ circumcisions, graftskin possesses a dermis, epider-mis and structural matrix like normal human skin tissue. In addition to skin replacement, tissue en-gineering has created cartilage replacements. Autologous cultured chondrocytes (Carticel) is an approved product/procedure to repair clinically significant, symptomatic painful knee cartilage da-mage (medial, lateral, or trochlear) caused by acute or repetitive trauma. The patient’s orthopedic surgeon sends the manufacturer a biopsy of the patient’s own cartilage, which is then cultured for reinjection into the knee.

Tissue engineers are actively exploring ways to create specialized tissues and vital organs. An exciting approach is the use of a scaffold made from a biodegradable polymer matrix shaped to fit the need (e.g., in the shape of a nose or an ear, etc.). An important pharmaceutical area of study is the use of hydrogels for scaffold development (Lee and Mooney, 2001). The patient’s own cells, donor cells orengineered cells are used to seed the scaffold. The cell-seeded scaffold is treated with requisite growth factors and placed in an appropriate growth environ-ment so that the cells can multiply and differentiate into the appropriate different cell types. The biopoly-mer degrades after transplantation providing func-tioning tissue or organ.

Currently, there are several clinical trials under-way testing novel technologies to replace damaged bone. Transgenic pigs and other animals are being engineered to provide organs for xenotransplantation to human patients that do not cause the immune system to initiate rejection mechanisms. Methodologies to introduce genes into patients to repair tissues “on-site” are being studied. Another area of active investigation is the development of technologies that can rejuvenate old tissues by manipulation of the cell’s own aging mechanisms.