Potential Applications

Potential Therapeutic Application

Source Umbilical Cord Lining
Type of Stem Cells Mesenchymal Stem Cells (MSCs) Cord Lining Epithelial Stem Cells (CLEpSCs)

Potential Treatment for

Tissue Repair

  • Cardiovascular diseases (e.g. cardiac muscle repair)
  • Orthopaedic applications (osteoarthritis, cartilage and tendon repair)
  • Pulmonary fibrosis1
  • Stroke2,3
  • Neurodegenerative disease:
    • Alzheimer's disease
    • Parkinson’s disease
  • Developmental disorder:
    • Autism Spectrum Disorder (ASD)4,5,6
    • Cerebral palsy and paralysis
    • Global Developmental Delay
  • Spinal cord injury7
  • Liver regeneration from liver failure8,9,10

HSCs Engraftment Support11

  • Shorten time of engraftment
  • Reduce immune system complications

Immune Modulation or Reconstitution12

  • Prevention and treatment of Graft vs Host Disease (GvHD)13
  • Diabetes type 1 & 214
  • HIV15
  • Crohn’s disease16

Wound/Soft Tissue Repair

  • Disorder of upper respiratory system
    e.g. repair and regeneration of bronchial epithelium for smokers
  • Surface ulcer (diabetic)
  • Various types of burns17
  • Tissue trauma
  • Skin wounds
  • Epidermal reconstitution18

Organ Lining Regeneration

  • Liver lining
  • Pancreatic lining
  • Gastrointestinal lining

Eye19

  • Corneal dermoid
  • Corneal scars and opacities
  • Corneal ulcers
  • Dry eye syndromes
  • Eye injury (e.g. chemical burn)
  • Limbal deficiency
  • Limbal corneal insufficiency syndrome
  • Macular degenerative diseases:
    • Age related myopia
    • Stargardt’s macular dystrophy
  • Ocular surface disease
  • Pterygium
  • Ocular damage due to Stevens Johnson Syndrome

Today, more than 1,27620 (as of September 2020) clinical trials are on-going worldwide to uncover the potential applications of umbilical cord lining stem cells. Thus far, encouraging results have been published; stem cell treatments have been proven safe and capable of repairing damage caused by stroke and heart disease. MSCs have also been used in combination with HSCs as a dual therapy to promote faster engraftment of HSCs and to reduce immune system complications21.

Although evidence has shown that Epithelial Cells (ECs) can be derived from MSCs, this does not diminish the importance of Cord Lining Epithelial Stem Cells  (CLEpSCs).

CLEpSCs are naive stem cells derived from the umbilical cord lining with the ability to differentiate into all different EC types such as skin, cornea, lining of the gut, etc on demand. ECs, on the other hand, have already reached terminal differentiation and cannot further change into different EC types when needed.

Thus, it is recommended to store both MSCs and CLEpSCs as they cannot be replaced by each other.

References




1 Chuang HM, Shih TE, Lu KY, et al. Mesenchymal Stem Cell Therapy of Pulmonary Fibrosis: Improvement with Target Combination. Cell Transplant. 2018;27(11): 1581–1587. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6299195/
2 Wang F, Tang H, Zhu J, Zhang JH. Transplanting Mesenchymal Stem Cells for Treatment of Ischemic Stroke. Cell Transplant. 2018;27(12):1825-1834 https://www.ncbi.nlm.nih.gov/pubmed/30251564
3 Xue P, Wang M, Yan G. Mesenchymal stem cell transplantation as an effective treatment strategy for ischemic stroke in asia: a meta-analysis of controlled trials. Ther Clin Risk Manag. 2018; 14: 909–928. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5957058/
4 Shane, et al. Do the Stem Cells Really Work with Autism Spectrum Disorders Associated with Neuro-Immune Interaction? Autism Open Access. 2015; 5(3) https://www.longdom.org/open-access/do-the-stem-cells-really-work-with-autism-spectrum-disorders-associatedwith-neuroimmune-interaction-2165-7890-1000151.pdf
5 Liu Q, Chen MX, Sun L, et al. Rational use of mesenchymal stem cells in the treatment of autism spectrum disorders. World J Stem Cells. 2019; 11(2): 55–72. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6397804/
6 Siniscalco D, Kannan S, Semprún-Hernández N, et al. Stem cell therapy in autism: recent insights. Stem Cells Cloning. 2018; 11: 55–67. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6204871/
7 Xu P, Yang X. The Efficacy and Safety of Mesenchymal Stem Cell Transplantation for Spinal Cord Injury Patients: A Meta-Analysis and Systematic Review. Cell Transplant. 2019; 28(1): 36–46. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322141/
8 Alfaifi M, Eom YW, Newsome PN, et al. Mesenchymal stromal cell therapy for liver diseases. J Hepatol. 2018;68(6):1272-1285. https://www.ncbi.nlm.nih.gov/pubmed/29425678
9 Maria P. de Miguel, I. Prieto, et al. Mesenchymal Stem Cells for Liver Regeneration in Liver Failure: From Experimental Models to Clinical Trials. Stem Cells International. 2019:3945672 https://www.hindawi.com/journals/sci/2019/3945672/
10 Wang YH, Wu DB, Chen B, et al. Progress in mesenchymal stem cell–based therapy for acute liver failure. Stem Cell Research & Therapy. 2018;9(1):227 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6109312/
11 Crippa S, Bernardo ME. Mesenchymal Stromal Cells: Role in the BM Niche and in the Support of Hematopoietic Stem Cell Transplantation. HemaSphere. 2018;2:6. https://journals.lww.com/hemasphere/Fulltext/2018/12000/Mesenchymal_Stromal_Cells__Role_in_the_BM_Niche.5.aspx
12 Damien P, Allan DS. Regenerative Therapy and Immune Modulation Using Umbilical Cord Blood-Derived Cells. Biol Blood Marrow Transplant. 2015;21(9):1545-54. https://www.bbmt.org/article/S1083-8791(15)00379-1/pdf
13 Zhao L, Chen S, Yang P, et al. The role of mesenchymal stem cells in hematopoietic stem cell transplantation: prevention and treatment of graft-versus-host disease. Stem Cell Research & Therapy. 2019; 10: 182 https://stemcellres.biomedcentral.com/articles/10.1186/s13287-019-1287-9
14 Clinical trials .Gov Website. Last accessed September 25, 2019 https://clinicaltrials.gov/ct2/results?cond=diabetes+mesenchymal+stem+cells&Search=Apply&recrs=b&recrs=a&recrs=f&recrs=d&recrs=e&age_v=&gndr=&type=&rslt=
15 Zhang Z, Fu J, Xu X, et al. Safety and immunological responses to human mesenchymal stem cell therapy in difficult-to-treat HIV-1-infected patients. AIDS. 2013; 27(8): 1283–1293 https://www.ncbi.nlm.nih.gov/pubmed/23925377
16 ClinicalTrials.org registry… NCT01090817, NCT01157650, NCT01659762, NCT00294112, NCT00482092, NCT03901235, NCT03449069, NCT00543374, NCT03220243, NCT02445547. Last accessed September 25, 2019
17 ClinicalTrials.org registry… NCT02904941, NCT03162367, NCT00856934, NCT00832156,NCT02145130, NCT03227146, NCT03229564, NCT02948023, NCT04030754, NCT03754218, NCT01655407, NCT02947737, NCT02765737, NCT00548314, NCT02325843, NCT03048188, NCT03913481, NCT02779205, NCT03791710, NCT02577861, NCT03686449. Last accessed September 25, 2019
18 Huang L, Wong YP, Gu H, et al. Stem cell-like properties of human umbilical cord lining epithelial cells and the potential for epidermal reconstitution. Cytotherapy. 2011;13:145–55. https://www.ncbi.nlm.nih.gov/pubmed/20735166
19 ClinicalTrials.org registry… NCT00459290, NCT00841581, NCT03916679,NCT03687632,NCT03608293, NCT02586883, NCT01722656, NCT00003704, NCT00667641, NCT02573324, NCT01166763, NCT01376349, NCT00999531, NCT00335491, NCT03519178, NCT00291135, NCT01635231. Last accessed September 25, 2019
20 Clinical Trials website. https://clinicaltrials.gov/ct2/results?term=mesenchymal&age_v=&gndr=&type=Intr& . Last accessed September 8 2020.
21 Battiwalla M, Hematti P. 2010. Cytotherapy. 1 January 2010.

Worldwide researches on diseases treated with MSCs by various Universities or Research Institutions:

Diseases Name of Universities/Research Institutions
Acute Graft vs Host Disease University of Kansas Medical Center, Kansas City, United States1
Alzheimer’s disease Samsung Medical Center, Seoul, Korea2
Cerebral palsy Duke University Medical Center, North Carolina, United States3
Chronic ischemic cardiomyopathy Nanjing University Medical School, Nanjing, China4
Diabetes Type 1
  • University Medical School, Nanjing, China5
  • Van Hanh General Hospital, Ho Chi Minh, Vietnam6
Diabetes Type 2 Van Hanh General Hospital, Ho Chi Minh, Vietnam7
Left ventricular dysfunction Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China8
Liver failure Xijing Hospital of Digestive Diseases, Shaanxi, China9
Osteoarthritis Universitas Indonesia, Jakarta, Indonesia10
Parkinson's disease University of Jordan, Amman, Jordan11
Rheumatoid arthritis
  • Stem Cell Institue, Panama City, Panama12
  • Xijing Hospital, Shaanxi, China13
  • Chonnam National University Hospital,
    Gangdong Kyung Hee University Hospital,
    Konkuk University Medical Center,
    Kyung Hee University Hospital,
    Seoul National University Boramae,
    Seoul National University Hospital, Seoul, Korea14
Spinal cord injury
  • Hospital de Neurorehabilitació, Barcelona, Spain15
Knee osteoarthritis Liaocheng City People's Hospital, Shandong, China16
Systemic lupus erythematosus Medical University of South Carolina, Charleston, United States17


References




1 Clinical Trials website. https://clinicaltrials.gov/ct2/show/NCT03158896. Last accessed September 25, 2019.
2 Clinical Trials website. https://clinicaltrials.gov/ct2/show/NCT02054208. Last accessed September 25, 2019.
3 Clinical Trials website. https://ClinicalTrials.gov/show/NCT03473301. Last accessed September 25, 2019.
4 Clinical Trials website. https://ClinicalTrials.gov/show/NCT02635464. Last accessed September 25, 2019.
5 Clinical Trials website. https://clinicaltrials.gov/ct2/show/NCT02763423. Last accessed September 25, 2019.
6 Clinical Trials website. https://clinicaltrials.gov/ct2/show/NCT03484741. Last accessed September 25, 2019.
7 Clinical Trials website. https://ClinicalTrials.gov/show/NCT03943940. Last accessed September 25, 2019.
8 Clinical Trials website. https://ClinicalTrials.gov/show/NCT03902067. Last accessed September 25, 2019.
9 Clinical Trials website. https://clinicaltrials.gov/ct2/show/NCT03668171. Last accessed September 25, 2019.
10 Clinical Trials website. https://clinicaltrials.gov/ct2/show/NCT03800810. Last accessed September 25, 2019.
11 Clinical Trials website. https://clinicaltrials.gov/ct2/show/NCT03684122. Last accessed September 25, 2019.
12 Clinical Trials website. https://clinicaltrials.gov/ct2/show/NCT01985464. Last accessed September 25, 2019.
13 Clinical Trials website. https://clinicaltrials.gov/ct2/show/NCT03798028. Last accessed September 25, 2019.
14 Clinical Trials website. https://ClinicalTrials.gov/show/NCT03618784. Last accessed September 25, 2019.
15 Clinical Trials website. https://clinicaltrials.gov/show/NCT03003364. Last accessed September 25, 2019.
16 Clinical Trials website. https://clinicaltrials.gov/show/NCT03166865. Last accessed September 25, 2019.
17 Clinical Trials website. https://clinicaltrials.gov/show/NCT02633163. Last accessed September 25, 2019.


Worldwide researches on diseases treated with Epithelial Cells (ECs) by various Universities or Research institutions

Diseases Name of Universities/Research Institutions
Skin wound Singapore General Hospital Burn Centre
Ocular surface disorders
  • Singapore Eye Research Institute
  • Kyoto Prefectural University of Medicine, Japan
Persistent epithelial defect National Eye Institute, Hanoi, Vietnam

DCR No. 4219, Version B, January 2021