1. Summer 2007 Workshop in Biology and Multimedia for High School Teachers

2. Why Can’t We Grow New Arms? An Introduction to Stem Cells and Regeneration Image by mila zinkova from commons.wikimedia.org http://en.wikipedia.org/wiki/Image:Sea_star_regenerating_legs.jpghttp://en.wikipedia.org/wiki/Image:Sea_star_regenerating_legs.jpg, image by Mila Zankova

3. Greek myth says that zeus had prometheus chained to a rock for bringing fire to humans. Every day an eagle would come and eat his liver. By the time the eagle came back the next day, the liver had grown back. Your liver can regenerate too! Will There be a day When your arm or leg will grow back? http://commons.wikimedia.org/wiki/Image:Koeln_wrm_1044.jpg

4. You have probably heard that sea stars can grow a new arm if they lose one, or even that a lost arm can grow into a whole new sea star. “Why can’t we grow new arms?” Did you know that salamanders can also regenerate lost limbs? This probably makes you wonder:

5. In order to answer that question, You will need to understand a little bit about how the salamander is able to regrow an arm and how your arm is formed in the first place.

6. Lesson Outline I. What are stem cells and where do they come from? II. How does a salamander regenerate a lost arm? III. Why can’t we grow a new arm? IV. What do stem cells have to do with limb development and regeneration? V. Can stem cells be used to grow new limbs? These are the questions you should be able to answer by the end of this lesson. As you proceed through the lesson, click on the green links to answer the questions on your worksheet. As you scroll over the links, some of them have instructions as to where on the page you should look for the answers.

7. I. What are stem cells and where do they come from? A.You have undoubtedly heard of stem cells. They are in the news all the time, but what exactly is a stem cell? http://commons.wikimedia.org/wiki/Image:Mouse_embryonic_stem_cells.jpg Mouse embryonic stem cells Learn about stem cells Answer question 1

8. I. What are stem cells and where do they come from? B. There are two types of stem cells, embryonic and adult. Find out how both are isolated, some similarities, and some differences. Embryonic vs. Adult Stem Cells Where the cells are found Pluripotent, embryonic stem cells originate as inner mass cells with in a blastocyst. The stem cells can become any tissue in the body, excluding a placenta. Only the morula's cells are totipotent, able to become all tissues and a placenta. http://commons.wikimedia.org/wiki/Image:Stem_cells_diagram.png Answer question 2

9. II. How Does a salamander Regenerate a Lost Arm? A. Imagine if humans could grow new limbs after amputation. Some salamanders can do just that. Read about limb regeneration in salamanders Visual of limb regeneration in salamander Limb Regeneration Movie Photograph taken by Patrick Coin http://commons.wikimedia.org/wiki/Image:Plethodon_cylindraceusPCCA20060409-3183A.jpg Answer questions 3-6

10. II. How Does a salamander Regenerate a Lost Arm? B. Review the basic steps of limb regeneration 1. An epidermal layer covers the wound. 2. Cells in the stump become unspecialized and accumulate under the epidermis. This structuure is the blastema. 3. The blastema elongates and flattens while cells are differentiating. 4. Finally new bones form and the limb pattern is back to normal. 5. The new limb grows and looks just like a normal limb.

11. III. Why Can’t We Grow a New Arm? A. First take a look at how a vertebrate limb develops in the first place. Vertebrate Limb Development Answer questions 7-9

12. III. Why Can’t We Grow a New Arm? As you can see, creating an arm is a very complex process that requires a number of different genes. Each step can trigger the next, and more and more genes and environmental factors get involved. http://commons.wikimedia.org/wiki/Image:Limb_bud.png org by Peter Znamenski

13. III. Why Can’t We Grow a New Arm? B. It is still unclear why salamanders can regenerate limbs while mammals and other vertebrates cannot. C. It may have something to do with the complexity, but there is more to it than that. Why do we form a scar instead of a new limb? Answer question 10

14. IV. What do stem cells have to do with limb development and regeneration? Now that you know what stem cells are, how a limb develops and how a salamander’s limb can regenerate, you may be wondering… What do stem cells have to do with limb development and regeneration?

15. IV. What do stem cells have to do with limb development and regeneration? A. Remember that stem cells are cells that can self-renew and make cells that can differentiate. This image shows how a hematopoietic stem cell (an adult blood stem cell) can differentiate into all of the different types of blood cells. http://stemcells.nih.gov/info/basics/basiImagehttp://stemcells.nih.gov/info/basics/basiImage courtesy of HINcs4.asp

16. IV. What do stem cells have to do with limb development and regeneration? B. In order for limbs (or any other body part) to develop, the stem cells must receive the proper signals. Each organ requires different signals or a different order of signals. So, during development, stem cells for blood will receive different information than those for skin or neurons. To get a better Idea of this concept play the virtual stem cell laboratory from children’s Hospital boston Answer questions 11-12

17. IV. What do stem cells have to do with limb development and regeneration? C. In salamander limb regeneration, it is unclear whether stem cells are involved, but it is known that there are some in the tissue that may contribute. D. We know that when a human muscle is damaged stem cells are responsible for repair.

18. IV. What do stem cells have to do with limb development and regeneration? E. Put together all of the information you now have about stem cells, development, and regeneration to figure out what scientists might want to research in order to promote limb growth in humans. Answer question 13.

19. This leads us to our final question…

20. V. Can Stem Cells Be Used to Grow a New Arm? A. Many scientists are working on this problem right now. They are studying frogs, salamanders, sea stars, and even mice to figure out how they can regenerate limbs or other body parts. Image by emo_boy from http://www.abstractinfluence.com/forums/album_pic.php?pic_id=8414 Image from http://commons.wikimedia.org/wiki/Image http://commons.wikimedia.org/wiki/Image :Mus_Musculus-huismuis.jpg#file commons.wikimedia.org http://commons.wikimedia.org/wiki/Image:Spiral_Salamander.jpg#file Photo Credit:US National Oceanic and Atmospheric Administration http://upload.wikimedia.org/wikipedia/commons/b/b1/Reef0296.jpg

21. Now find an article about studies into limb regeneration. Read the Article and write down the source. Then, summarize the article and hand it in with your “Stem Cells and Regeneration” worksheet. end Extension, Learn More, References

22. extension I. Why are some people opposed to stem cell research? II. How do I feel about stem cell research and use? Use some of the links below to answer question I. Then, write about your own opinions. Be sure to explain how you feel and give reasons for your opinion.

23. Learn More If you would like more information on stem cells, regeneration or development, go back to any of the links in this presentation or check out some of the following: The book Mutants by Armand Marie Leroi discusses human development through mutation. It is full of interesting stories and science. http://www.unews.utah.edu/p/?r=050306-6 - article about research grant at University of Utah http://www.unews.utah.edu/p/?r=050306-6 http://www.regen.iupui.edu/research_appendage.asp - information about research on limb regeneration at Indiana University http://www.regen.iupui.edu/research_appendage.asp http://discoverysedge.mayo.edu/regenerative_biology/index.cfm - online research magazine from the mayo clinic http://discoverysedge.mayo.edu/regenerative_biology/index.cfm http://www.mirm.pitt.edu/ - McGowan Institute for Regenerative Medicine From University of Pittsburgh http://www.mirm.pitt.edu/ http://www.isscr.org/public/selected_topics.htm - International Society for Stem Cells http://www.isscr.org/public/selected_topics.htm http://stemcell.stanford.edu/101/ - Stanford Institute for Stem Cell biology and Regenerative Medicine http://stemcell.stanford.edu/101/ http://www.hsci.harvard.edu/ - Harvard Stem Cell Institute http://www.hsci.harvard.edu/

24. References Amphibian Limb Regeneration http://www.uoguelph.ca/zoology/devobio/210labs/regen1.html http://www.uoguelph.ca/zoology/devobio/210labs/regen1.html Commons.wikimedia.org Morrison, Jamie L. et al “Salamander limb regeneration involves the activation of a multipotent skeletal muscle satellite cell population” JCB 30 January 2006 http://www.jcb.org/cgi/content/full/172/3/433http://www.jcb.org/cgi/content/full/172/3/433 Salamanders Re-grow Lost Limbs, Could Human Medicine Benefit From Understanding Regeneration? Science Daily 1 April 2007 http://www.sciencedaily.com/releases/2007/03/070330111307.htmhttp://www.sciencedaily.com/releases/2007/03/070330111307.htm Stem Cell Basics: What are adult stem cells?. In Stem Cell Information [World Wide Web site]. Bethesda, MD: National Institutes of Health, U.S. Department of Health and Human Services, 2006 [cited Wednesday, July 18, 2007] Available at http://stemcells.nih.gov/info/basics/basics4http://stemcells.nih.gov/info/basics/basics4 Stocum, David L. Biology and Medicine: An Overview 1 July 2004 http://www.cellscience.com/Reviews1/Regenerative_Biology_and_Medicine.html http://www.cellscience.com/Reviews1/Regenerative_Biology_and_Medicine.html Vertebrate Limb Development--an Example of the Development of Body Parts http://www.indiana.edu/~oso/evolution/limbs.htm http://www.indiana.edu/~oso/evolution/limbs.htm