Umbilical Cord Blood (UCB) is fresh and ethical source of effective stem cells. Cord Blood derived stem cells are considered most ethical type of adult stem cells because the Cord Blood is regarded as a waste tissue and hence the use of stem cells from the Cord Blood is endorsed by religious groups including the Roman Catholic Church.
Stem cells are unspecialized cells that have the remarkable ability to self-renew without changing their properties and differentiate into various specialized types of cells and tissues under right conditions and environment. They are the baseline cells in embryos to develop into a full-grown individual. There are two broad types of stem cells derived from a human that have been studied in depth; (1) Embryonic Stem cells vs. (2) Adult Stem cells.
Embryonic stem cells vs Adult stem cells
Embryonic Stem Cells
Embryonic Stem (ES) cells are the cells derived from the inner cell mass of blastocyst – an early stage of fertilized egg before implantation; in humans, blastocyst stage can be achieved in 4~5 days after fertilization. The ES cells have the remarkable ability to self-renew in their undifferentiated state indefinitely and to differentiate into any types of mature cells under the guided condition. For these reasons, ES cells have been studied extensively in the past decades for possibilities of developing therapies for diseases [11] [12].
However, there are several reasons that ES cells are not yet suitable for therapeutic use, both scientifically and ethically. Due to its ability to differentiate into any type of cells, ES cells not only differentiate into the desired cell types but may also turn into tumor cells [13]. Possibility of tumor formation raises a safety issue for ES cells to be used in cell-based therapy. The preparation of any human ES cells also raises an ethical issue, as human ES cells are collected through destruction of human embryos – a living form of an early human with distinct identity. For this reason, Roman Catholic Church is banning the use of ES cells for any kind of research or cell-based therapy [14].
Adult Stem Cells
Adult stem cells are not fully differentiated cells found in human body. Many adult tissue types in human body contain their own stem cells – muscles, blood, liver, intestine, bone marrow etc, in order to repair damaged tissue or replenish used cells. They are also found in the umbilical cord blood (the blood contained within the umbilical cords obtained following childbirth), which is a rich source of stem cells that are no longer needed.
Adult stem cells are considered to be similar to ES cells in their multipotency (ability to differentiate into multiple cell types) without any ethical issues on destruction of a human embryo. Furthermore, unlike ES cells, they are limited in their capacity to differentiate into different cell types and self-renew, hence much lower possibility of tumor formation [15].
For more than a decade, human adult stem cells have been extensively studied for therapeutic use and there are more than 4,000 ongoing clinical trials around the world using adult stem cells of various sort for treatments for diseases such as osteoarthritis, cardiac diseases, diabetes, GVHD etc. and this number is actively growing [16].
Vatican’s Support and Promotion on Adult Stem Cell Research and Cell-based Therapy
In 2010, Vatican’s Pontifical Council of Culture and NeoStem (a commercial company engaged in the development and manufacturing of cell-based therapies), have engaged a partnership to advance adult stem cell research with their non-profit organizations STOQ International (Science, Theology and the Ontological Quest) and the Stem for Life Foundation (SFLF). It was considered as a “necessary union between Science and Faith”. The initiative brought the partners together to raise awareness and advancing scientific work on adult stem cells, exploring clinical application for regenerative medicine and examining its cultural impact – a work that will lead to a fundamental shift in medical treatment from managing illnesses to developing cures through cellular therapies [17] [18].
Here is their mission statement [19]:
“To discuss and understand the importance of scientific advancements in the paradigm shift toward regenerative medicine, with a particular focus on adult stem cell therapies and the interconnections between research, faith, ethics and culture.”
Since the collaboration, the Vatican has hosted two International Stem cell Conferences in 2011 and 2013 [20] focusing on scientific research and clinical application of adult stem cells in Regenerative Medicine while sharing the sensitivity of the ethical values for protecting human life at any stage of its existence. At both meetings, leading experts and foremost leaders of Church, adult stem cell research, medicine, ethics, public policy, education and stem cell therapeutic business community from around the world as well as Ambassadors to the Holy See were gathered together to discuss the future of stem cell research and its clinical application as well as ongoing medical advancements occurring throughout the world.
The collaboration of Science and Church also accomplished several other initiatives such as [21]:
• A special edition of the Pontifical Council for Culture’s quarterly journal, Cultures and Faith. It published works by many of the leaders in stem cell research.
• Publication of a book about adult stem cells, The Healing Cell: How the Greatest Revolution in Medical History Is Changing Your Life, released in April 2013.
• E-learning initiative for adult stem cells is being prepared to reach the public, Catholic and non-Catholic education institutions, and others. It contains online curriculum about adult stem cells, developing therapies, and the cultural impact of this research.
The Vatican further showed support by recognizing the scientist for his work in developing stem cell therapies [22] and a 14 year-old girl whose life has been transformed after receiving adult stem cell therapy for her fragile bones [23]. These demonstrate the Vatican’s support for promoting adult stem cell research and therapy as an ethically and scientifically promising approach for regenerative medicine.
Over 15 years of researchers has demonstrated safety and effectiveness of UCB-derived stem cells with multiple publications in the high-profile scientific and medical journals.
Through rigorous Research and Development efforts since 2001, MEDIPOST & SAMSUNG Medical Center partnership has developed CARTISTEM® with consistent large-scale manufacturing of CARTISTEM® as a biological drug product by regulatory authority in Korea which can be prescribed to any patient universally.
CARTISTEM® is the world’s first allogeneic stem cell product with Biologics License Application (BLA) approved by the Ministry of Food and Drug Safety (MFDS) Korea (formerly known as the Korea FDA) for the regeneration of knee cartilage for the sufferers of degenerative osteoarthritis (OA). CARTISTEM® contains multi-potent human Umbilical Cord Blood-derived Mesenchymal Stem Cells (hUCB-MSCs) which have very unique characteristics including not provoking an immune-response when transplanted into unrelated recipients. This allows large-scale manufacturing of CARTISTEM® using freshly isolated MSCs from the voluntarily donated cord blood units. Cultured MSCs can then be stored frozen as a Drug Substance (DS) until a prescription is received from the clinics. The allogeneic nature of CARTISTEM® delivers a truly ‘industrial scale’ cell therapeutics with a concept of a ‘drug’ in both Chemistry-Manufacture-Control (CMC) for mass manufacturing and logistical advantages compared to other cell therapeutics such as cell products using cells of autologous-origin.
CARTISTEM® is a cryo-preserved (frozen), adult stem cell product containing cord blood-derived Msenchymal Stem Cells (MSCs) and hence enables instant availability of the stem cell drugs without invasive collection from a patient’s own tissue(s). Although CARTISTEM is a, ready-to-use drug, it is prepared/manufactured according to the regulatory-approved protocols, which takes approximately 6 months to complete. Cartistem is further processed from its frozen state into live stem cells, which has to be used with 2 days from release at the GMP facility.
Benefits of using CARTISTEM® – an adult stem cell product
CARTISTEM® was developed by MEDIPOST Co Ltd for the treatment of osteoarthritis (OA). CARTISTEM® is comprised of human Mesenchymal Stem Cells (MSCs) collected from Umbilical Cord Blood (UCB) – a material normally would be discarded as a medical waste after childbirth. MSCs are type of adult stem cells that can differentiate into several types of cells such as osteoblast (bone cells), chondrocytes (cartilage cells) and adipocytes (fat cells)[24] [25], making them an excellent source for cartilage repair in OA patients.
There are several advantages of using cord-blood derived CARTISTEM®
• Cord-blood is collected from veins attached to placenta, after an umbilical cord has been detached from a child. In most cases, these umbilical cords are disposed without further use after childbirth.
• The collection method for cord-blood is not harmful either for the baby or the mother. It is the least invasive method of collecting blood for stem cells, compared to the collection methods for other types of adult stem cells from tissues such as bone marrow.
• Although CARTISTEM® is comprised of MSCs derived from the cord-blood of a newborn, the MSCs are still considered as “adult” stem cells because they are not from the embryonic origin. Use of adult stem cell does not violate any ethical or religious values that protect rights of human life and it is strongly supported by the Roman Catholic Church.
• While cord-blood contains many types of cells other than the MSCs, such as red and white blood cells, CARTISTEM® is comprised of ONLY the MSCs with high purity and therefore the therapeutic efficacy for OA is very high.
• The MSCs collected from the cord-blood for CARTISTEM® are considered to be the youngest adult stem cells that can be harvested. It has been suggested that the MSCs from younger donors exerted better therapeutic efficacy than those from the old donors [26].
CARTISTEM® is manufactured under strict regulatory observation in Korea which ensures safe and consistently efficacious stem cell product is delivered to patients. Since 2012, over thousands releases of CARTISTEM® stem cell product has been made without a single safety issue or adverse event reported in Korea.
The manufacturing of the hUCB-MSC drugs start with the raw material – human Umbilical Cord Blood, voluntarily donated by the consented donors. The cord blood is then subjected to Infectious Disease Testing (IDT) and other eligibility tests followed by culture. Once the cells are cultured up to a certain Passage (or population doubling) stage the cells are frozen and stored as the Drug Substance (DS) until the prescription is received from the hospitals or clinics. The frozen DS is then thawed and prepared into the final CARTISTEM® Drug Product (DP).
[11] Thomson J. A., Itskovitz-Eldor, J, Shapiro, SS, Waknitz, MA, Swiergiel, JJ, Marshall, VS, Jones, JM (1998). Embryonic Stem Cell Lines Derived from Human Blastocysts. Science 282 (5391): 1145–1147.
[12] http://stemcells.nih.gov/info/basics/
[13] Andres, P (2002) From teratocarcinomas to embryonic stem cells. Philos Trans R Soc Lond B Biol Sci 357(1420): 405–417
[15] Young, H. E. and Black Jr, A. C. (2004) Adult Stem Cells Anat Rec A Discov Mol Cell Evol Biol 276A:75–102
[16] https://clinicaltrials.gov/
[19] http://adultstemcellconference.org/2011/
[20] http://adultstemcellconference.org/
[21] http://adultstemcellconference.org/about/the-initiative/
[23] http://www.pe.com/articles/stem-670911-cells-elizabeth.html
[24] Phinney D. G. and Prockop D. J. (2007). “Concise review: mesenchymal stem/multipotent stromal cells: the state of transdifferentiation and modes of tissue repair—current views”. Stem Cells 25 (11): 2896–902
[25] Nardi, N. Beyer, da Silva Meirelles, L. (2006). “Mesenchymal Stem Cells: Isolation, In Vitro Expansion and Characterization”. In Wobus, Anna M.; Boheler, Kenneth. Stem Cells. Handbook of experimental pharmacology 174. pp. 249–82
[26] Li, L., Guo, Y., Zhai, H., Yin, Y., Zhang, J., Chen, H., Wang, L., Li, N., Liu, R. and Xia, Y (2014) Aging increases the susceptibility of MSCs to reactive oxygen species and impairs their therapeutic potency for myocardial infarction PLoS One 9(11): e111850