Wharton’s Jelly Stem Cells: safety & more

stem cells from poweredtemplatesADVANTAGES OF WHARTON’S JELLY STEM CELLS ESPECIALLY MESENCYMALS (Designated as WJ-MSC for convenience below) ESPECIALLY WITH RESPECT TO SAFETY

 

 

WJ HAS MORE STEM CELLS THAN EITHER BONE MARROW OR ADIPOSE TISSUE

The quantity of mesenchymal stem cells which can typically be obtained from bone marrow is far less than that Wharton’s Jelly: 0.001 to 0.01% mononuclear cells from BM, with 1 g of adipose tissue yielding ~ 5 × 103 stem cells, and Wharton’s jelly 1 to 5 × 104 cells/cm of umbilical cord. In side-by-side comparison studies of MSC from bone marrow adipose tissue and Wharton’s jelly, WJ-MSCs had the highest proliferative capacity.

WJ STEM CELLS ARE MORE PRIMITIVE THAN OTHER ADULT STEM CELL TYPES YET DO NOT PRODUCE TUMORS AND ACTUALLY HAVE ANTI-TUMOR EFFECTS IN VITRO (Lab dish) AND IN VIVO (In living animals & humans)  

WJ-MSC differ from other adult MSCs with respect to the fact they demonstrate far more primitive characteristics e.g., they express embryonic-like stem cell markers including  pluripotency genes, Oct-4, Nanog, and SOX-2 but at levels well below that of embryonic stem (ESC) cells. Despite this, WJ-MSCs do not form tumors (teratomas). This is attributed to the fact that WJ-MS’s have a lower expression of pluripotency genes than embryonic stem cells (ESCs being very pluripotent and by virtue of this are prone to develop teratomas when injected into animals or humans). When WJ-MSCs were injected in immunocompromised and immunodeficient animals they still failed to form tumors.

Also: WJ-MSCs express low levels of the embryonic stem cell pluripotency markers POUF1, NANOG, SOX2 and LIN28, which also plays a role in the fact they do not produce teratomas. WJ-MSCs also synthesize and express several cytokines including IL12A which is associated with the induction of apoptosis (programmed cell death) which is believed to underlie their ability to lyse (eradicate) tumor cells.

Furthermore, the transcriptome of WJ-MSC and ESC differs substantially in that WJ-MSCs demonstrate high expression levels of several tumor suppressor genes and suppresses tumors both in vitro and in vivo. Moreover, large quantities of tumor growth inhibiting cytokines and growth factors are secreted by WJ-MSCs. Also, WJ-MSC cell lysates as well as the conditioned medium they are cultured in strongly inhibited the growth of breast adenocarcinoma, ovarian carcinoma, osteosarcoma, benign neoplastic keloid cells, bladder tumor, and lymphoma cells  in vitro. When WJ-MSC cell lysates and conditioned medium were injected into mammary carcinoma, osteosarcoma, and pancreatic and lung tumors it inhibited their growth and shrank the tumors in vivo .

WJ-MSCs DO NOT CAUSE IMMUNE REJECTION OR ADVERSE REACTIONS  

WJ-MSCs have also been found to be immunoprivileged which is to say they escape rejection or adverse immune reactions. Part of the reason for this lies in the fact WJ-MSCs have low MHC-I levels and an absence of MHC-II expression. And, though they synthesize low amounts of MHC class I, WJ-MSCs have no immunogenicity. Research indicates that this is due to the fact they  do not express costimulatory molecules such as CD 40, CD80, CD86, and also produce high levels of immune response inhibitors such as indoleamine-2,3-dioxygenase (IDO), prostaglandin E2 (PGE2) and leukocyte antigen G6 (HLA-G6).

NOVA CELLS INSTITUTE HARVESTS & MAKES CLINICAL USE OF STEM CELLS ISOLATED FROM (UMBILICAL CORD) WHARTON’S JELLY CELLS: https://ncimx.wordpress.com/2015/03/15/whartons-jelly-stem-cells/

ADDITIONAL REFERENCES – NIH PubMed results (5-1-2016)

Wharton’s Jelly-derived mesenchymal stem cells alleviate memory deficits and reduce amyloid-β deposition in an APP/PS1 transgenic mouse model.
Xie ZH, Liu Z, Zhang XR, Yang H, Wei LF, Wang Y, Xu SL, Sun L, Lai C, Bi JZ, Wang XY.
Clin Exp Med. 2016 Feb;16(1):89-98. doi: 10.1007/s10238-015-0375-0. Epub 2015 Jul 19.
PMID: 26188488 [PubMed – in process]
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Therapeutic influence of intraperitoneal injection of Wharton’s jelly-derived mesenchymal stem cells on oviduct function and fertility in rats with acute and chronic salpingitis.
Luo HJ, Xiao XM, Zhou J, Wei W.
Genet Mol Res. 2015 Apr 17;14(2):3606-17. doi: 10.4238/2015.April.17.10.
PMID: 25966129 [PubMed – indexed for MEDLINE] Free Article
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Effect of human Wharton’s jelly mesenchymal stem cell secretome on proliferation, apoptosis and drug resistance of lung cancer cells.
Hendijani F, Javanmard ShH, Rafiee L, Sadeghi-Aliabadi H.
Res Pharm Sci. 2015 Mar-Apr;10(2):134-42.
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Preserved β-cell function in type 1 diabetes by mesenchymal stromal cells.
Carlsson PO, Schwarcz E, Korsgren O, Le Blanc K.
Diabetes. 2015 Feb;64(2):587-92. doi: 10.2337/db14-0656. Epub 2014 Sep 9.
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. The Potential of Wharton’s Jelly Derived Mesenchymal Stem Cells in Treating Patients with Cystic Fibrosis.
Boruczkowski D, Gładysz D, Demkow U, Pawelec K.
Adv Exp Med Biol. 2015;833:23-9. doi: 10.1007/5584_2014_17. Review.
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Wharton’s jelly derived mesenchymal stem cells: future of regenerative medicine? Recent findings and clinical significance.
Kalaszczynska I, Ferdyn K.
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Undifferentiated Wharton’s Jelly Mesenchymal Stem Cell Transplantation Induces Insulin-Producing Cell Differentiation and Suppression of T-Cell-Mediated Autoimmunity in Nonobese Diabetic Mice.
Tsai PJ, Wang HS, Lin GJ, Chou SC, Chu TH, Chuan WT, Lu YJ, Weng ZC, Su CH, Hsieh PS, Sytwu HK, Lin CH, Chen TH, Shyu JF.
Cell Transplant. 2015;24(8):1555-70. doi: 10.3727/096368914X683016. Epub 2014 Jul 15.
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Effects of Wharton’s jelly-derived mesenchymal stem cells on neonatal neutrophils.
Khan I, Zhang L, Mohammed M, Archer FE, Abukharmah J, Yuan Z, Rizvi SS, Melek MG, Rabson AB, Shi Y, Weinberger B, Vetrano AM.
J Inflamm Res. 2014 Dec 31;8:1-8. doi: 10.2147/JIR.S71987. eCollection 2015.
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A comparison of Wharton’s jelly and cord blood as a source of mesenchymal stem cells for diabetes cell therapy.
El-Demerdash RF, Hammad LN, Kamal MM, El Mesallamy HO.
Regen Med. 2015;10(7):841-55. doi: 10.2217/rme.15.49. Epub 2015 Nov 6.
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. Comparisons of Differentiation Potential in Human Mesenchymal Stem Cells from Wharton’s Jelly, Bone Marrow, and Pancreatic Tissues.
Kao SY, Shyu JF, Wang HS, Lin CH, Su CH, Chen TH, Weng ZC, Tsai PJ.
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. Roles of the co-culture of human umbilical cord Wharton’s jelly-derived mesenchymal stem cells with rat pancreatic cells in the treatment of rats with diabetes mellitus.
Wang G, Li Y, Wang Y, Dong Y, Wang FS, Ding Y, Kang Y, Xu X.
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Comprehensive characterization of four different populations of human mesenchymal stem cells as regards their immune properties, proliferation and differentiation.
Li X, Bai J, Ji X, Li R, Xuan Y, Wang Y.
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Safety and feasibility of umbilical cord mesenchymal stem cells in treatment-refractory systemic lupus erythematosus nephritis: time for a double-blind placebo-controlled trial to determine efficacy.
Woodworth TG, Furst DE.
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A preliminary evaluation of efficacy and safety of Wharton’s jelly mesenchymal stem cell transplantation in patients with type 2 diabetes mellitus.
Liu X, Zheng P, Wang X, Dai G, Cheng H, Zhang Z, Hua R, Niu X, Shi J, An Y.
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Protein synthesis and secretion in human mesenchymal cells derived from bone marrow, adipose tissue and Wharton’s jelly.
Amable PR, Teixeira MV, Carias RB, Granjeiro JM, Borojevic R.
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Therapeutic effect of transplanted human Wharton’s jelly stem cell-derived oligodendrocyte progenitor cells (hWJ-MSC-derived OPCs) in an animal model of multiple sclerosis.
Mikaeili Agah E, Parivar K, Joghataei MT.
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Zou X, Zhang G, Cheng Z, Yin D, Du T, Ju G, Miao S, Liu G, Lu M, Zhu Y.
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. Effect of combined therapy of human Wharton’s jelly-derived mesenchymal stem cells from umbilical cord with sitagliptin in type 2 diabetic rats.
Hu J, Wang F, Sun R, Wang Z, Yu X, Wang L, Gao H, Zhao W, Yan S, Wang Y.
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Arno AI, Amini-Nik S, Blit PH, Al-Shehab M, Belo C, Herer E, Jeschke MG.
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