Assignment #2 - Scientific Paper Review

In vitro evaluation of the effects of human umbilical cord extracts on human fibroblasts, keratinocytes, and melanocytes

Phuc Van Pham & Loan Thi-Tung Dang &

Uyen Thanh Dinh & Huyen Thi-Thu Truong &

Ba Ngoc Huynh & Dong Van Le & Ngoc Kim Phan
2013

Introduction

When skin ages due to UV radiation, it is referred to as photoaging.  Photoaging occurs when fibroblasts and keratinocytes proliferation is inhibited, also collagen and fibronectin expression is inhibited.  It also activates collagenases, which breakdown collagen, such as matrix metalloproteinase-1. All of these factors cause wrinkles, the major characteristic of skin aging. Pham et al (2013) used intracellular umbilical cord extracts, extracellular umbilical cord extracts and umbilical cord-derived stem cell extracts to test the effects on fibroblasts, keratinocytes and melanocytes.  Fibroblasts are responsible for producing collagen in the dermis of the skin.  Keratinocytes make up 90% of the skins epidermis which is used for protection from pathogens, heat, UV radiation and water loss.  Melanocytes are located in the bottom layer of the epidermis which produce melanin. Melanin affects the pigment of your skin and absorbs UV light and prevents exposure to the dermis layer.

Figure 1: Skin aging

Figure 2: Young skin versus older skin

                  Figure 3: Melanocytes and Keratinocytes                          Figure 4: Fibroblasts in dermis

Results

Pham et al (2013) had very positive results with their experiment. They collected umbilical cords under consent and isolated the three skin cell types. Many experiments have been done with placental extracts on skin aging, but few from umbilical cord extracts.  There are at least four areas of the umbilical cord that are stem-cell rich.  These include the cord lining membrane, Wharton's jelly, umbilical cord vein and umbilical cord blood. Pham et al (2013) prepared 25 formulae, five being the control.  They found that 7.5% and 10% of formula 35 stimulated the proliferation of fibroblasts significantly more than the control.  Therefore, they chose the 7.5% for the optimal concentration to continue with the experiment.  Formula 35 contains both extracellular and intracellular umbilical cord extracts.  In the keratinocytes, 7.5% of formula 35 also increased the proliferation significantly more than the control.  Next, Pham et al (2013) tested formula 35 on collagen 1, fibronectin and MMP-1.  They found that this formula strongly inhibited MMP-1, while significantly stimulating collagen 1.  Formula 35 did not show a change in fibronectin or on the expression of tyrosinase, which is important in the synthesis of melanin. Overall, they proved that by stimulating keratinocyte and fibroblasts proliferation, they can inhibit MMP-1 and stimulate collagen 1, reducing skin aging.

                                                 Figure 5: The 25 formulae used by Pham et al (2013)

Critique

Overall, I think the paper was well done.  I found it very interesting because I have never heard of anything like this being done before. It was easy to follow and read because each section flowed into the next.  Although, at some points there was some information that went way over my head in the introduction and material and methods. There were many figures and tables that were very useful to help me understand a bit clearer. Also, both the experimental and control groups were compared and presented clearly.  I think that there was a good amount of samples and control groups, considering they only used protein extracts from three places. The only other negative I found was that they did not specifically state a hypothesis to their experiment.  I think it is amazing what cells from  umbilical cord extracts and stem cells from any part of the body can do.  As the research of both continues, I hope researchers find more breakthroughs for medical uses.

My Favourite Tissue - The Umbilical Cord


Basic Anatomy and Function 

The umbilical cord is what connects the developing fetus during pregnancy
to the placenta, which passes nutrients and other materials                              

between the mother and the fetus. Also, the fetus cannot breathe, therefore it provides the fetus with the oxygen it needs[2].  The umbilical cord is made up of two arteries and one vein.  The arteries carry blood from the fetus to the placenta and the vein carries blood back to the fetus. The arteries and veins are protected by a substance called Wharton's Jelly [1].  It is usually 1 inch in diameter and 23 inches in length and is coiled in a counterclockwise direction[1]. The origin of the umbilical cord is comprised of the yolk sac and
allantosis[2].                                                                                                                             Figure 1: Umbilical cord
                                                                                                                    

Figure 2: Developing fetus in the uterus

Figure 3: Anatomy of Umbilical Cord

Development of the Umbilical Cord

Between the 4th and 8th week of pregnancy, the amnion envelopes the body stalk, ductus omphalo-entericus and the umbilical coelom.  The amniotic cavity then surrounds the connecting stalk plus the embryo and presses the stalk into a tube-like structure that is covered in epithelium, connecting the developing embryo to the placenta. Eventually, all structures are lost except for the vein and arteries which are embedded in Wharton's Jelly[3].

                                                      Figure 4: Development of cord

Histology

The umbilical cord is composed of 

different types of epithelium throughout.  Near the navel is composed of unkeratinized, stratified squamous epithelium, which provides the transition 
from abdominal wall to the cord surface. Further away from the navel, it is composed of 2-8 layers of stratified columnar epithelium and also simple columnar epithelium[4].

Wharton's Jelly is composed of mucous connective tissue.  Fibroblasts are the most prominent cell type in connective tissue, which secretes the fibers, composing

the extracellular matrix.  These include collagen, elastic and reticular fibers and carbohydrate components,
such as GAG's[5].          



                                                           
                                                Figure 5: Cross section of umbilical cord






Figure 6: Fibroblasts in connective tissue




Pathology

Decreased length: An umbilical cord is considered short when it is 40 cm or less. A short umbilical cord is associated with fetal movement disorders, placental abruption and cord rupture, all which are to fatal to the fetus[6].

Increased Length: An umbilical cord is considered long when it is 70 cm or more. A long umbilical cord could cause fetal entanglement, true knots and thombi.  A long cord has been found to be associated with increased brain abnormalities. The cord can wrap around the babies neck and cut off the oxygen supply to the brain.  This is more common in males and occurs in 20-33% of pregnancies[6].

Knots: True knots occur in 1% of pregnancies and are usually caused by older maternal age and increased cord length.  True knots are associated with higher intrauterine death than those with normal cords. False knots are caused by an excessive amount of  localized Wharton's Jelly and are not clinically significant[6].

                                                             Figure 7: False knot (top) and true knot (bottom)
      


Cord Stricture:  This is a constriction of the umbilical cord and occurs in 19% of fetal deaths, as most are stillborn. They are caused by a deficiency in Wharton's jelly and there may be evidence that cord strictures could be genetic[7]. 

   
Hematoma: An umbilical hematoma is extravasation of blood into the Wharton's jelly surrounding the blood vessels. They can occur spontaneously and can be associated with cord cysts.  Hematoma's are responsible for 50% of fetal mortality[7].

Cysts: An umbilical cord cyst can be a true or false cyst and occur in 0.4% of pregnancies.  True cysts are caused by remnants of early embryonic structures.  False cysts are fluid-filled sacs that are related to swelling in the Wharton's jelly.  Some cysts can be associated with birth defects, such as chromosomal abnormalities and kidney defects[7].

                                                                               Figure 8: Umbilical cyst


Interesting Facts

• The umbilical cord contains hematopoietic stem cells, which can become specialized cells to help treat leukaemia, lymphoma and other diseases!

• Babies will touch and play with their umbilical cord while in utero and will even suck on it

References

Herer, Elaine and Blott, Maggie. (2009). Pregnancy Day by Day. Retrieved from
http://pregnancy.familyeducation.com/prenatal-health-and-nutrition/fetal-growth-and-development/66161.html [1]

Cloe, Adam. (2013). What are 3 Functions of the Umbilical Cord?. Retrieved from
http://www.ehow.com/about_4672809_what-functions-umbilical-cord.html [2]

Life Map. (2012). Embryonic Development. Retrieved from http://discovery.lifemapsc.com/in-vivo-development/umbilical-cord [3]

Baergen, Rebecca., Benirschke, Kurt and Kaufmann, Peter. (2006). Pathology of the human
placenta, 5th edition. Springer New York. pp 380-451 [4]

Volkoff, Helene. (2013). Histology: Connective Tissue. (Power Point slides). [5]

Beall, Marie. (2012). Umbilical Cord Complications. Retrieved from http://emedicine.medscape.com/article/262470-overview#aw2aab6b3[6]

March of Dimes. (2013). Umbilical Cord abnormalities. Retrieved from http://www.marchofdimes.com/pregnancy/umbilical-cord-abnormalities.aspx[7]

Images:

1. http://library.med.utah.edu/WebPath/PLACHTML/PLAC012.html
2. http://m.medlineplus.gov/ency/presentations/100196.htm
3. http://misskalypso.wordpress.com/2011/05/05/cord-around-the-neck-no-worries/
4. http://radioguraphics.net/tt?page=4
5.http://lecannabiculteur.free.fr/SITES/UNIV%20W.AUSTRALIA/mb140/CorePages/Connective/Connect.htm
6. http://www.vetmed.vt.edu/education/curriculum/vm8054/Labs/Lab5/Lab5.htm
7. http://www.jacknaimsnotes.com/2011/09/false-vs-true-umbilical-cord-knot.html
8. http://newborns.stanford.edu/PhotoGallery/WhartonJellyCyst1.html