Potential Applications

Mesenchymal Stem Cells (MSCs)

Tissue repair

  • Cardiovascular diseases (e.g. cardiac muscle repair)
  • Orthopaedic applications (osteoarthritis, cartilage and tendon repair)
  • Pulmonary fibrosis1
  • Stroke2,3
  • COVID-1922
  • 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

HSC engraftment support11

  • Shorten time of engraftment
  • Reduce immune system complications

Immune modulation or reconstitution12

  • COVID-1922
  • Prevention and treatment of Graft vs Host Disease (GvHD)13
  • Diabetes type 1 & 214
  • HIV15
  • Crohn's disease16

Cord Lining Epithelial Stem Cells (CLEpSCs)

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 regeneration

  • Liver23,24
  • Pancreas25,26
  • Gastrointestinal Tract27,28

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

As of September 2020, there are more than 1,276 clinical trials going on around the world to find out what umbilical cord lining stem cells could be used for.20 So far, encouraging results have been published. It has been shown that stem cell treatments are safe and capable of repairing damage caused by stroke and heart disease. HSCs have also been used with MSCs as a dual therapy to promote faster engraftment of HSCs and to reduce immune system complications.21

Even though there is evidence that epithelial cells (ECs) can be derived from MSCs, this does not make Cord Lining Epithelial Stem Cells (CLEpSCs) less important.

CLEpSCs are naive stem cells that come from the lining of the umbilical cord. They can turn into any type of EC on demand, such as skin, cornea, the lining of the gut, and so on. On the other hand, ECs have already reached terminal differentiation and are unable to change into different EC types.

Thus, we recommend you store both MSCs and CLEpSCs because they cannot replace 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): 15811587. 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: 909928. 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): 5572. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6397804/
6 Siniscalco D, Kannan S, Semprn-Hern¡ndez N, et al. Stem cell therapy in autism: recent insights. Stem Cells Cloning. 2018; 11: 5567. 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): 3646. 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;13:14555. 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.
22Afarid M, Sanie-Jahromi F. Mesenchymal Stem Cells and COVID-19: Cure, Prevention, and Vaccination. Stem Cells International 2021. 2021;0705:1-12
23Lim R, Hodge A, Moore G, et al. A Pilot Study Evaluating the Safety of Intravenously Administered Human Amnion Epithelial Cells for the Treatment of Hepatic Fibrosis. Front Pharmacol. 2017; 8:549.
24Lim RHG, Liew JXK, Wee A, et al. Safety Evaluation of Human Cord-Lining Epithelial Stem Cells Transplantation for Liver Regeneration in a Porcine Model. Cell Transplant. 2020 Jan-Dec; 29:963689719896559.
25Lebreton F, Lavallard V, Bellofatto K, et al. Insulin-producing organoids engineered from islet and amniotic epithelial cells to treat diabetes. Nat Commun. 2019; 10, 4491.
26Zhou Y, Gan SU, Lin G, et al. Characterization of Human Umbilical Cord Lining-Derived Epithelial Cells and Transplantation Potential. Cell Transplantation. 2011; 20(11-12):1827-1841.
27Fujino A, Cuchimoto Y, Mori T, et al. Evaluation of safety and efficacy of autologous oral mucosa-derived epithelial cell sheet transplantation for prevention of anastomotic restenosis in congenital esophageal atresia and congenital esophageal stenosis. Stem Cell Res Ther. 2023; 14, 86.
28Kanetaka K, Eguchi S. Regenerative medicine for the upper gastrointestinal tract. Regenerative Therapy. 2020; 15, 129-137.

Worldwide research on diseases treated with MSCs by various universities and research institutions:
DiseasesName of Universities/Research Institutions
Acute Graft vs Host DiseaseUniversity of Kansas Medical Center, Kansas City, United States1
Alzheimer's diseaseSamsung Medical Center, Seoul, Korea2
Cerebral palsyDuke University Medical Center, North Carolina, United States3
Chronic ischemic cardiomyopathyNanjing University Medical School, Nanjing, China4
Diabetes Type 1University Medical School, Nanjing, China5
Van Hanh General Hospital, Ho Chi Minh, Vietnam6
Diabetes Type 2Van Hanh General Hospital, Ho Chi Minh, Vietnam7
Left ventricular dysfunctionShanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China8
Liver failureXijing Hospital of Digestive Diseases, Shaanxi, China9
OsteoarthritisUniversitas Indonesia, Jakarta, Indonesia10
Parkinson's diseaseUniversity of Jordan, Amman, Jordan11
Rheumatoid arthritisStem 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 injuryHospital de Neurorehabilitació, Barcelona, Spain15
Knee osteoarthritisLiaocheng City People's Hospital, Shandong, China16
Systemic lupus erythematosusMedical 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 research on diseases treated with epithelial cells (ECs) by various universities and research institutions
DiseasesName of Universities/Research Institutions
Skin woundSingapore General Hospital Burn Centre
Ocular surface disordersSingapore Eye Research Institute
Kyoto Prefectural University of Medicine, Japan
Persistent epithelial defectNational Eye Institute, Hanoi, Vietnam

DCR No. 4525, Version C, January 2022.