TECHNOLOGY COLUMNColumn Editor: Karen Goldschmidt MSN, RNC

Journal of Pediatric Nursing (2013) 28, 504–507

Tissue Engineering With Stem Cells: An I

nnovative Technological Treatment inPediatrics DisordersCheryl Mele MSN, PNP, BC, AC/PC, NNP, BC⁎Drexel University

Karen Goldschmidt MSN, RNC

"Inspired by the lackof organ transplantdonors available,research is under-way on developingstem cells for regen-erative medicine ortissue engineering."

A TWO-YEAR-old girl named Hannah Warren, fromSeoul, South Korea was born without a trachea a conditionreferred to as tracheal agenesis. Dependent upon a ventilator,Hannah spent the first two years of her life in the hospital.Physicians in Seoul determined that standard surgicaltreatment was not an option for correcting her trachealdefect. Upon further investigation into stem cell research, themedical team located an Italian physician named Dr. PaoloMacchiarini, who was creating tracheas on a scaffold withstem cells for adult patients (Fitzgerald, 2013). In May 2013,with little hope remaining, Hannah’s parents agreed to a newsurgical intervention. Hannah received a tracheal transplant;however, the trachea implanted was one created from stemcells taken from her bone marrow.

Tracheal agenesis is a very rare condition; only 1 in50,000 children are born with the disorder (Fitzgerald, 2013).Nonetheless, by employing tissue engineering, a particularstem cell technique similar to the procedure illustrated inHannah’s case, children with birth defects may have apromising future (Figure 1). The article will explore newtechnologies in stem cell transplants such as tissueengineering utilized in pediatric patients.

Types of Stem Cells Used in TissueRegeneration

Stem cells have the unique ability to self-regenerate, havea decreased risk of rejection, and distinguish themselves into

⁎ Corresponding author: CherylMele,MSN, PNP, BC,AC/PC,NNP,BC.E-mail address: cm3242@drexel.edu.

0882-5963/$ – see front matter © 2013 Elsevier Inc. All rights reserved.http://dx.doi.org/10.1016/j.pedn.2013.07.002

specific types generally due to some kind of signal (Koch,Berg, & Betts, 2009). Stem cells originate from two primarysources adult stem cells (non-embryonic) or embryonic cells.

Non-embryonic stem cells are re-sultant of somatic cells that exist allover the body and originate indiverse types of tissue such asskin, the brain, bone marrow, skel-etal muscle, and liver (Crosta,2013). Non-embryonic cells canself-refurbish and differentiate intoa variety of cell types. It was firstthought that non-embryonic cellswere restricted in their capability todifferentiate based upon their orig-inal organ, but there is an indication that this may not be the case (Crosta, 2013). Adulthematopoietic stem cells, non-embryonic stem cells fromblood, bone marrow or cord blood, have been used tosuccessfully treat hematological cancers (i.e. bone marrowused for the treatment of leukemia, and lymphomas).

There are a variety of adult stem cells acknowledged invarious organs and tissues of the body. Within the previousdecade, progenitor cells (early descendants of stem cells)have been found in an array of adult tissues such as thegastrointestinal tract, brain, skin, and muscle (Aboushwareb& Atala, 2008). Progenitor stem cells can differentiate intomany cell types but are unable to replicate indefinitely;however, research has shown potential relevance to amultitude of disorders in building heart valves, blood vesselsand muscular tissue (Aboushwareb & Atala, 2008).

Mesechenchymal cells (MSCs) which are derived fromthe bone marrow’s stromal cells grow easily in a culture dishand can form into other cells such as costeocytes (bone cells),

Figure 1 Girl with stem cell trachea repair. Reprinted from Two year old girl born without a windpipe receives artificial trachea grown fromstem cells: by Fitzgerald (2013). Medical News Today, retrieved from http://ww.medicalnewstoday.com/articles/259942.php. Printed withpermission.

505Stem Cells

adipocytes (fat cells), or chondrocytes (cartilage cells)(Evans, Gentleman, & Polak, 2006) (Figure 2). MSCs havenatural healing properties (immune and immunomodulatoryproperties) that make them an attractive option for treatment(Monaco, Bionaz, Hollister, & Wheeler, 2011). There aremany examples of scientific research where MSCs havedifferentiated into other roots, including heart cells, livercells, and neurons. In addition, MSCs have the potential to

Figure 2 Diagram demonstrating how adult stem cells can be used in tisin a culture dish. Adherent mesenchymal stem cells can then be expandedwith permission from Evans et al. (2006). Scaffolds for stem cells, Mate

provide treatment for spinal cord injury, neurologicalischemia, regeneration of heart muscle, and ocular disease(Evans et al., 2006; Kuo, Ho, & Lee, 2009). However, thereare limitations to the application of MSCs. MSCs can onlydivide a restricted number of times, which reduces theirlifespan and differentiation potential (Khan, 2010). Anadditional drawback is that the older the donor, the lesseffective the MSCs will perform.

sue engineering. Marrow is removed from the adult bone and placedor directed to differentiate into bone, cartilage, or fat cells. Reprintedrials Today, 9 (12), 26-33.

Table 1 Different Types of Stem Cells and Potency

Stem Cell Type Characteristics Source

Totipotent Differentiate into all cell types in all living tissue Fertilized egg or embryoPluripotent Differentiate into many kinds of tissue Embryonic stem cells and cells resultant from mesoderm,

endoderm and ectoderm germ layers that form in the beginningstage of embryonic cell differentiation (7 day embryo)

Multipotent Only differentiate into one tissue type Hematopoietic or bone marrow cells (adult) stem cellsUnipotent Only differentiate or produce their own cell type,

but the ability to renewBone cells and muscle stem cells

Note: Table Adapted from Crosta (2013). What are stem cells? Medical News Today, Retrieved from http://www.medicalnewstoday.cominfo/stem- cell.Printed with permission.

506 C. Mele

Embryonic stem cells (ESCs), in contrast to adult stemcells are able to divide indefinitely and can differentiate intoany tissue of the body, making ESCs an exceptional celltype. ESCs are primitive and derived from 5-day-oldembryos in the blastocyst stage of development (Fitzgerald,2013). These unique cell mass called totipotent cells canarise to any of the three-embryonic germ layers (ectoderm,mesoderm, and endoderm) and are thought to act as theprimary repair bodies for related organs (Aboushwareb &Atala, 2008). There are various types of stem cells with

Figure 3 An illustration outlining the potential for tissue engineering. Sin culture. They can then be either seeded directly on a scaffold or differencell type before seeding on the scaffold. Cell seeded scaffolds can then bebody. Reprinted with permission from Scaffolds for stem cells by Evans

different characteristics and potency (Table 1). Geneticmanipulation is also an effective technique for conductingthe differentiation of ESCs and has been found to be aneffective treatment for neurological disorders (Evans et al.,2006). However, there is much controversy surrounding theuse of Human ESCs. ESCs are limited in their use not onlydue to the potential immunological problems that theyinduce; in addition, there are several ethical, political, andlegal controversies that arise from using those (Aboushwareb& Atala, 2008).

tem cells can be derived from embryos or adult tissues and expandedtiated in culture and sorted to obtain a purified population of a targetgrown in culture to develop a desired tissue prior to implanting in theet al. (2006). Materials Today, 9 (12), 26-33.

507Stem Cells

Tissue Engineering and Clinical Applications

Inspired by the lack of organ transplant donors available,research is underway on developing stem cells for regener-ative medicine or tissue engineering. Tissue engineeringinvolves seeding stem cells into live isolated cells andpersuading them to grow into a three-dimensional scaffold(Guillot, Cui, Fisk, & Polak, 2007). Tissue engineering is aninterdisciplinary field intended for the maintenance, restora-tion or replacement of malfunctioning organs (Guillot et al.,2007). Clinical trials on methods to regenerate bladder,kidney, and urethra tissue in children are already underway(Aboushwareb & Atala, 2008). Further applications of tissueengineering have been applied in cases of bone loss due todisease or trauma, but it has its limitations. Bone grafting, thecurrent standard of practice in bone disease has its limitationsmaking the utilization of scaffolds derived from stems cells amore appealing application (Monaco et al., 2011) (Figure 3).

Future Perspectives

Tissue engineering may emerge into future prospects suchas congenital heart disease and gastrointestinal disorders. It isknown that the alimentary tract is a highly specialized organsystem and the loss of any bowel segment can becatastrophic to a child. Medical and surgical treatments fornecrotizing entercoloitis, trachea-esophageal fistula (TEF),or hirschsprungs disease are often suboptimal. However, inmice model experiments, utilizing stem cell tissue, engi-neering strategies enabled growth of full thickness tissue andthe restoration of normal function of the autologoussyngeneic tissue (Levin & Grikscheit, 2012). Thus, in thefuture it may be possible to fully engineer a human colon,trachea, and anus for the restoration of normal gastrointes-tinal function in congenital defects. Most of the tissueengineering in cardiac disorders has focused on valvular andblood vessel repair. Additionally, mesenchymal and plurip-otent stem cells have been actively cultivated in tocontracting myocardial tissue and bioartificial cardiac tissuein neonatal mice, offering hope to irreversible pediatric heartconditions (Bernstein & Srivastava, 2012).

In summary, the past decade imparted comprehension ofstem cell biology and applications in various pediatricdisorders. Although the challenge of how to assemble athree-dimensional scaffold tissue from stem cells remainsunperfected; some organ regeneration has been quitesuccessful. The main focus of researchers working with

tissue engineering has been to design, direct, and enhancecell function in order to prevent rejection (Evans et al.,2006). Nurses need to obtain a basic knowledge of differentstem cell types utilized in medical and surgical managementof patients as technology advances. Stem cell therapyapplications have expanded beyond standard hematopoietictherapies. Some of the newer, technologies described in thisarticle have gone from the bench to the bedside, especially inthe urological and orthopedic realm with many innovativeapplications on the horizon.

As for Hannah Warren, she ended her fight for life on July6, 2013, three months after receiving a tracheal transplantmade from her own stem cells (Johnson, 2013). Hannahreportedly died of complications unrelated to her transplant.She suffered from an esophageal tear and subsequent lungcomplications. The medical community views Hannah’stransplant procedure as an innovation that advanced thescience of stem cell treatment for all patients.

References

Aboushwareb, A., & Atala, A. (2008). Stem cells in urology. NatureClinical Practice, 5, 621–631.

Bernstein, H., & Srivastava, D. (2012). Stem cell therapy in cardiac disease.Pediatric Research, 71, 491–499.

Crosta, P. (2013). What are stem cells?Medical News Today Retrieved fromhttp://www.medicalnewstoday.com/info/stem-cell.

Evans, N., Gentleman, E., & Polak, J. (2006). Scaffolds for stem cells.Materials Today, 9, 26–33.

Fitzgerald, K. (2013). Two-year-old girl born without a windpipe receivesartificial trachea grown from stem cells. Medical News Today Retrievedfrom http://ww.medicalnewstoday.com/articles/259942.php.

Guillot, P., Cui, W., Fisk, N., & Polak, D. (2007). Stem cell differentiationand expansion for clinical applications of tissue engineering. Journal ofCellular and Molecular Medicine, 11, 935–944.

Johnson, C. K. (2013). Hannah Warren dead: Toddler who receivedwindpipe made from stem cells dies. Huffington Post Retrieved from.http://www.huffingtonpost.com/2013/07/08/hannah-warren-stem-cell-windpipe-dead-dies_n_3562922.html?ir=Healthy+Living.

Khan, W. (2010). Forward: Stem cell application and tissue engineeringapproaches in sports medicine- from bench to bedside. Journal of StemCells, 5, 150–154.

Koch, T., Berg, L., & Betts, D. (2009). Current and future regenerativemedicine- Principles, concepts, and therapeutic use of stem cell therapyand tissue engineering in equine medicine. The Canadian VeterinaryJournal. La revue Veterinaire Canadienne, 50, 155–165.

Kuo, T., Ho, J., & Lee, O. (2009). Mesenchymal stem cell therapy for non-musculoskeletal diseases: Emerging technologies. Cell Transplantation,18, 1013–1028.

Levin, D., & Grikscheit, T. (2012). Tissue engineering of the gastrointestinaltract. Current Opinion in Pediatrics, 17, 365–370.

Monaco, E., Bionaz, M., Hollister, S. J., & Wheeler, M. B. (2011).Strategies for regeneration of the bone using porcine adult adipose-derived mesenchymal stem cells. Theriogenology, 75, 1381–1399.