An Introduction to Tissue Engineering

Cindy Handley, PhD, MT(ASCP)SCCC Biology Instructor

Acknowledgements:•Pittsburgh Tissue Engineering Initiative

a network strategy to promote regional economic growth through the advancement and creation of biomedical and related technologies associated with engineered tissues, Including cell culturing, gene therapy, organ transplantation and regeneration, biomaterials, and computer-assisted analysis and design. http://www.ptei.org/

•Mark Krotec, BS, MS facilitator for the summer teachers’ workshop and major

contributor of data for this presentation via the Education Outreach Manual in Tissue Engineering and the summer workshop.

Overview

I. Tissue engineering defined

II. Stem cell research

III. Tissue model constructs

and lab techniques

IV. Ethics

I. Tissue Engineering Defined

“Tissue engineering is an emerging

interdisciplinary field that applies

the principles of biology and

engineering to the development of

viable substitutes that restore,

maintain, or improve the function of

human tissues.”

According to the Pittsburgh Tissue Engineering Initiative,

What are ‘viable substitutes’?

• On a large scale, certain surgical interventions, like castration of a bull, have led to alteration of tissue function.

• On a molecular level, gene therapy is has been very successful with plants and animals

• On a cellular level, the research is currently focused on stem cells.

Stem cells

According to the Merriam-Webster Online Dictionary, a stem cell is,

“an unspecialized cell that gives rise to differentiated cells“

Two basic types:Embryonic – pluripotentialAdult – multipotential

Embryonic stem cells

According to Richard Mollard, Ph.D., of the International Society for Stem Cell Research, “Human embryonic stem (ES) cells are cultured cell lines derived from the inner cell mass of the blastocyst that can be grown indefinitely in their undifferentiated state, yet also are capable of differentiating into all cells of the adult body.”

http://www.time.com/time/2001/stemcells/#

• Animation: Stem cells

http://www.dnalc.org/stemcells.html

Embryonic stem cells (con’t)

• Two sources– Fertilized egg from in vitro fertilization– Ovum that has had nucleus removed

and nuclear material injected from intended recipient of final tissue product

(reproductive/therapeutic cloning)

• Very controversial

Adult stem cells

• Found in:– Umbilical cord blood/tissue– Adult brain, blood cornea, retina, heart,

fat, skin, dental pulp, bone marrow, blood vessels, skeletal muscle and intestines

II. Stem cell research

What progress has been madeto date?

• Autologous stem cells have been injected into heart to regenerate damaged cardiac tissue

• Corneal autologous stem cell grafts have been used to treat eye disease & trauma

• Skin replacement has been grown with stem cells for transplant in burn victims

Progress…

• Autologous stem-cell cartilage grafts have been used to treat joint disease

• Leukemia & other cancers have been treated with stem cells from bone marrow and umbilical cord blood

• A human mandible has been produced using a titanium mesh and autologous bone-marrow stem cells

The future?

According to the Stem Cell Research Center:Half Of All Americans Could Benefit From Stem Cell ResearchExperts are predicting that stem cell research has the potential to help up to half of all Americans, who suffer from some form of presently incurable disease, injury or birth defect. Some of Those conditions include:

One million children with juvenile diabetes 8.2 million people with cancer 58 million with heart disease Four million suffering from Alzheimer's disease 10 million with osteoporosis 43 million arthritis sufferers 250,000 people paralyzed by spinal cord injuries 30,000 victims of Lou Gehrig's disease 500,000 with Parkinson's disease

www.stemcellresearchfoundation.org/WhatsNew/Benefit.htm

III. Tissue model constructs &

lab techniques

Tissue engineering requires three things:

Cells

SignalsScaffold

• We’ve already discussed different types of cells that may be used

• The scaffold refers to the matrix within the tissue model construct

• The signals refer to molecular signaling molecules, also known as growth factors

Basic scaffold criteria:

• Portions need to be biodegradable

• Usually designed in the shape of the tissue product the researcher is working on

www.eng.nus.edu.sg/ EResnews/0210/rd/rd_10.html

Biomimetic Scaffold Fabrication

                                                                                                                                       

bms.dent.umich.edu/research/malab.html

www.millenium-biologix.com/Html/00_ScientificInformationCartiGraft.htm

Autologous de novo cartilage formed on Skelite™ tissue engineering scaffold (grown in vitro), illustrating the configuration of the implant that provides functional cartilage tissue at the articular surface. The presence of functional cartilage tissue represents a major advance over current cell therapy techniques. Cell therapy involves the implantation of cells that still have to make new cartilage in vivo at the defect site under very challenging conditions. The histology image on the right shows that cells are healthy and growing, while attaching themselves to the Skelite™ and beginning to differentiate into mature cartilage.

V. Ethics

Now that we see that we CAN, the question is…

should we??????

ETHICS

• The great divide over stem cells (www.mtulode.com/index.php?issuedate=&section=12&artid=4540)

• The Ethics of Human Embryonic Stem Cell Research (www.isscr.org/public/ethics.htm)

• Research Ethics and Stem Cells (stemcells.nih.gov/info/ethics.asp)

Ethics (con’t)

• Stem Cell Research: All sides to the dispute (www.religioustolerance.org/res_stem.htm)

• Guidelines for Human Embryonic Stem Cell Research(www.iom.edu/report.asp?id=26661)

SUMMARY

I. Tissue engineering defined

II. Stem cell research

III. Tissue model constructs

and lab techniques

IV. Ethics

Selected References Cited

Armon, C. (2005) Medscape Neurology & Neurosurgery 7(1), 2005. Retrieved September 18, 2005, from http://www.medscape.com/viewarticle/496732

Bhatia, R., & Hare, J. (2005). Mesenchymal Stem Cells: Future Source for Reparative Medicine [Electronic version]. Congestive Heart Failure, 11(2), 87-91.

Carmichael, Mary. (2005). Organs under construction. Newsweek, Summer 2005, 46-48.

Lanza, R., & Rosenthal, N. (2004). The Stem Cell Challenge. Scientific American, June 2004, 93-99.

Pittsburgh Tissue Engineering Initiative (2001). An Education Outreach manual in Tissue Engineering, updated through June 2005. Pittsburg, PA, PTEI: Author.

Weiss, R. (2005). The power to divide. National Geographic. July 2005, 3-27.