Wharton’s Jelly THOUSANDS OF DIFFERENT …...Materials & Methods (continued) One Umbilical Cord...

Wharton’s JellyTHOUSANDS OF DIFFERENT

PROTEINS AND PEPTIDES

Proteomic Analysis of Umbilical Fluid Wharton’s Jelly: A Comprehensive Data Set

Juan Arellano Jr.(a), Esmaeil Dehghan, Ph.D.(b) ,Mohammed Goodarzi, Ph.D.(c), Andrew Lemoff, Ph.D.(d) One Umbilical Cord Lab(a), Senior Research Associate(b), Instructor(c) ,UT Southwestern Medical Center, UTSW Dallas, Texas; Director, Proteomics

Core Facility,Assistant Professor, Department of Biochemistry(d)

Key Words. Wharton’s Jelly • Umbilical Cord • Therapy • Proteomics Abstract

The human umbilical cord, a rich source of mesenchymal stromal tissue, is a conduit between the developing embryo and the placenta to provide a source of fetal nourishment. Many scientists and clinicians are increasingly interested in the mucoid connective tissue of the human umbilical cord, Wharton’s jelly.[1] The reasons are the noninvasive harvest from tissue normally discarded at birth, the relatively high tissue yields and a phenotype that parallels that of mesenchymal stromal tissue from other tissue sources. Several recent reviews have highlighted the efficacy of umbilical cord-derived tissues and their potential advantage over other sources.[2] We propose the most extensive analysis of the human umbilical cord. Our study identifies an extensive catalog of over 2,000 proteins that conclude Wharton’s jelly possesses the earliest available access for tissue regeneration.

Introduction The human umbilical cord has become an increasingly used source of mesenchymal stromal tissues for tissue therapy in regenerative medicine.[5] The structure appears simple, with an outer covering of a single layer of amniotic epithelium that encloses a mucoid connective tissue, Wharton’s jelly, through which three vessels, a vein and two arteries, carry oxygenated and deoxygenated blood between the placenta and fetus respectively.[2] Wharton’s jelly, first described by Thomas Wharton in 1656, is unique among connective tissues as it contains only mesenchymal tissues that comprise the functional myofibroblasts of the tissue, and their precursors. There are no other tissue types described in Wharton’s jelly, and no vascular or nervous elements, except the three major vessels of the cord itself.[6] Studies conclude that 95% of Wharton’s jelly is extracellular matrix comprising collagen (3.6), glycoprotein(0.3), hyaluronin (0.31), sulfated glycosaminoglycan (0.14), and diffusible plasma proteins (1.2) - all % wet weight.[1] Until recently, little was known about Wharton’s jelly in the human umbilical cord. This is the first key study of proteins, from a proteomic observation, to catalog the molecular characteristics of proteins. This study is the foundation to begin to identify more proteins in Wharton’s jelly such as subsets of proteins, peptides, and growth factors.[7] Although this study is a rough overview of what is to be discovered upon further analysis in the future, it provides a first ever point of establishment. The study concludes that Wharton’s jelly is an important connective tissue in the future of regenerative medicine, providing highly effective and safe treatment for tissue regeneration.

Materials & Methods To better understand the functions of individual proteins and their place in complex biological systems, it is necessary to measure changes in protein abundance relative to those of the system. As a result, modern proteomics has shifted from its initial qualitative outlook and currently encompasses a continuum of qualitative and quantitative technologies and approaches. The field of proteomics demands state-of-the-art sample preparation techniques, analytical technologies, and software solutions.

© 2019 University of Texas Southwestern Medical Center and One Umbilical Cord Lab

Materials & Methods (continued) One Umbilical Cord Lab is an ISO 5 certified laboratory, FDA registered (#3013913163), and regulated by FDA Article 21 CFR Part 1271 and The Joint Commission Standard QC.5.310.7. The donor blood samples were tested for all relevant FDA required infectious diseases by an independent CLIA accredited laboratory. The results of the following tests are NEGATIVE: HIV type 1 and type 2, Hepatitis B surface antigen, Hepatitis B core antigen, Hepatitis C virus and Syphilis. The umbilical cord tissue samples were prepared by One Umbilical Cord Lab. The tissue samples were kept in the original packaging , stored at -80* C in an ultra-low temperature freezer until ready for protein analysis by the University of Texas Southwestern Medical Center Proteomics Core Facility in Dallas, Texas.

In the analysis, proteins were extracted from samples, and disulfide bond reduction and alkylation were performed using tris(2-carboxyethyl)phosphine hydrochloride (TCEP)and iodoacetamide (IAA). The sample was loaded onto a micro S-Trap column (PROTIFI) and digested overnight with trypsin. Peptides were eluted from the S-trap and dried in a SpeedVac. Solid-phase extraction cleanup was performed with an Oasis HLB µ elution plate (Waters), and the resulting peptides were reconstituted in 2% (v/v) acetonitrile (ACN) and 0.1% trichloracetic acid in water. [4]

A fraction of these samples were injected onto an Orbitrap Fusion Lumos mass spectrometer (ThermoElectron) coupled to an Ultimate 3000 RSLC-Nano liquid chromatography system (Dionex). Samples were injected onto a 75 um i.d., 75-cm long EasySpray column (Thermo), and eluted with a gradient from 0-28% buffer B contained 80% (v/v) ACN, 10% (v/v) trifluoroethanol, and 0.1% formic acid in water. The mass spectrometer operated in positive ion mode with a source voltage of 1.5-2.4kV and an ion transfer tube temperature of 275 ºC. MS scans were acquired at 120,000 resolution in the Orbitrap, and up to 10 MS/MS spectra were obtained in the ion trap for each full spectrum acquired using higher-energy collisional dissociation (HCD) for ions with charges 207. Dynamic exclusion was set for 25 s after an ion was selected for fragmentation. [4]

Results Raw MS data files were analyzed using Proteome Discoverer v2.2 (Thermo), with peptide identification performed using Sequest HT searching against the human database from UniProt. Fragment and precursor tolerant yes of 10 ppm and 0.5 Da were specified, and three missed cleavages were allowed. Carbamidoe`methylation of Cys was set as a fixed modification and oxidation of Met as a variable modification. The false discovery rate (FDR) cutoff was 1% for all peptides. [4] The Proteomic Analysis yielded detailed definitions of the most abundant proteins and were modeled with a three dimensional diagram are shown in Figure 1.

The proteomic analysis continued with over 2,000 proteins identified in the umbilical cord samples. The results of the University of Texas Southwestern Medical analysis identify the sensitivity at 99% (High) . The # of Peptide Spectrum Matches (PSM’s) for the protein identifies the total # of peptide sequences present for that particular protein including the protein molecular weight (MW). Results of this analysis were collected in a data sheet and shown in Table 1.






Figure 1: Above: The definition of the most abundant proteins with a three dimensional diagram. Proteomic analysis by UTSW: definition of the top ten proteins [3]

A: Serum albumin (ALB) is produced in the liver and is the most abundant blood protein in mammals. Serum albumin transports hormones, fatty acids and other compounds, buffers ph, and maintains oncotic pressure, around other functions. B: Immunoglobulin heavy constant gamma 1 (IGHG1) is a constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. C: ACTC1 encodes cardiac muscle alpha actin. Alpha cardiac actin is the major protein of the thin filament in cardiac sarcomeres, which are responsible for muscle contraction and generation of force to support the pump function of the heart. D: Transgelin (TAGLN) is a protein that in humans is encoded by the TAGLIN gene and is a transformation and shape change sensitive actin cross-linking/gelling protein found in fibroblasts and smooth muscle. E: Transferrins (TF) are iron-binding blood plasma glycoproteins that control the level of free iron (Fe) in biological fluids. Human transferrin is encoded by the TF gene. F: Filamin A, alpha (FLNA) is an actin-binding protein, 280-kD protein, that crosslinks actin filaments into orthogonal networks in cortical cytoplasm and particulates in the anchoring of membrane proteins for the actin cytoskeleton. Remodeling of the cytoskeleton is central to the modulation of tissue shape and migration. G: Alpha-1-antitrypsin (A1AT,A1A, or AAT) is a protein belonging to the serpin superfamily. A protease inhibitor, it protects tissues from enzymes of inflammatory tissues, especially neutrophil elastase. H: Lumican (LUM) is a proteoglycan Class II of the small leucine-rich protestlycan (SLRP) family. It includes decor, biglycan, fibromodulin, keratocan, epiphycan, and osteoglycin. Lumican is a major keratin sulfate proteoglycan of the cornea but is ubiquitously distributed in most mesenchymal tissues through the body. It is also involved in collagen fibril organization and circumferential growth, corneal transparency and epithelial tissue migration and tissue repair. I: Troponyosin 1 alpha chain encoded by the TPM1 gene and is a member of the tropomyosin family of highly conserved, widely distributed actin-binding proteins involved in the contractile system of striated and smooth muscles and the cytoskeleton of non-muscle tissues. J: Immunoglobulin kappa constant , also known as IGKC, is a human gene that encodes the constant domain of kappa-type-light chains for antibodies. It is found on chromosome 2 in humans. Secreted immunoglobulins mediate the effector phase of humoral immunity, which results in the elimination of bound antigens.




Table 1: University of Texas Southwestern Medical Center Proteomic Analysis Samples 1-25. The human umbilical cord samples prepared by One Umbilical Cord Lab, Inc. analyzed by University of Texas Southwestern as defined in the table below (Detailed spreadsheet available upon request.) [4]

#P.FDRC.C

Master Accession DescriptionCov.[%]

# PSMsMW

[kDa]Abundance

% Abu.

1 High M.Protein P02768 Serum albumin OS=Homo sapiens OX=9606 GN=ALB PE=1 SV=2 88 2055 69.3 112,494,043,342.5 39.24

2 High M.Protein A0A0A0MS08Immunoglobulin heavy constant gamma 1 (Fragment) OS=Homo sapiens OX=9606 GN=IGHG1 PE=1 SV=1 52 322 43.9 16,524,331,373.6 5.76

3 High M.Protein P68032Actin, alpha cardiac muscle 1 OS=Homo sapiens OX=9606 GN=ACTC1 PE=1 SV=1 86 319 42.0 16,187,654,956.9 5.65

4 High M.Protein Q01995 Transgelin OS=Homo sapiens OX=9606 GN=TAGLN PE=1 SV=4 82 245 22.6 11,486,174,029.8 4.01

5 High M.Protein P02787 Serotransferrin OS=Homo sapiens OX=9606 GN=TF PE=1 SV=3 75 260 77.0 9,645,961,604.8 3.36

6 High M.Protein P21333 Filamin-A OS=Homo sapiens OX=9606 GN=FLNA PE=1 SV=4 70 309 280.6 7,361,603,762.2 2.57

7 High M.Protein A0A024R6I7Alpha-1-antitrypsin OS=Homo sapiens OX=9606 GN=SERPINA1 PE=1 SV=1

68 195 46.7 5,293,236,749.6 1.85

8 High M.Protein P51884 Lumican OS=Homo sapiens OX=9606 GN=LUM PE=1 SV=2 48 104 38.4 3,907,161,270.6 1.36

9 High M.Protein Q6ZN40Tropomyosin 1 (Alpha), isoform CRA_f OS=Homo sapiens OX=9606 GN=TPM1 PE=1 SV=1 61 108 37.4 2,940,598,369.0 1.03

10 High M.Protein P01834Immunoglobulin kappa constant OS=Homo sapiens OX=9606 GN=IGKC PE=1 SV=2 80 94 11.8 2,916,149,951.9 1.02

11 High M.Protein P60709Actin, cytoplasmic 1 OS=Homo sapiens OX=9606 GN=ACTB PE=1 SV=1 86 239 41.7 2,791,785,304.4 0.97

12 High M.Protein P17936Insulin-like growth factor-binding protein 3 OS=Homo sapiens OX=9606 GN=IGFBP3 PE=1 SV=2 30 7 31.7 2,454,501,304.6 0.86

13 High M.Protein P02647 Apolipoprotein A-I OS=Homo sapiens OX=9606 GN=APOA1 PE=1 SV=1 69 82 30.8 2,259,927,056.0 0.79

14 High M.Protein P12814 Alpha-actinin-1 OS=Homo sapiens OX=9606 GN=ACTN1 PE=1 SV=2 78 124 103.0 2,076,330,717.0 0.72

15 High M.Protein P06733 Alpha-enolase OS=Homo sapiens OX=9606 GN=ENO1 PE=1 SV=2 74 136 47.1 2,074,814,841.6 0.72

16 High M.Protein P18206 Vinculin OS=Homo sapiens OX=9606 GN=VCL PE=1 SV=4 70 137 123.7 1,978,048,677.8 0.67

17 High M.Protein A0A0B4J231Immunoglobulin lambda-like polypeptide 5 OS=Homo sapiens OX=9606 GN=IGLL5 PE=1 SV=1

36 26 23.1 1,919,787,054.0 0.65

18 High M.Protein P69905Hemoglobin subunit alpha OS=Homo sapiens OX=9606 GN=HBA1 PE=1 SV=2 84 52 15.2 1,858,433,261.3 0.65

19 High M.Protein P69891Hemoglobin subunit gamma-1 OS=Homo sapiens OX=9606 GN=HBG1 PE=1 SV=2

84 43 16.1 1,851,552,511.8 0.58

20 High M.Protein P01023Alpha-2-macroglobulin OS=Homo sapiens OX=9606 GN=A2M PE=1 SV=3 67 123 163.2 1,658,177,187.3 0.58

21 High M.Protein P00338L-lactate dehydrogenase A chain OS=Homo sapiens OX=9606 GN=LDHA PE=1 SV=2

76 55 36.7 1,649,282,610.0 0.57

22 High M.Protein P02751 Fibronectin OS=Homo sapiens OX=9606 GN=FN1 PE=1 SV=4 48 109 262.5 1,630,342,486.5 0.55

23 High M.Protein P04406Glyceraldehyde-3-phosphate dehydrogenase OS=Homo sapiens OX=9606 GN=GAPDH PE=1 SV=3 77 115 36.0 1,575,809,272.5 0.54

24 High M.Protein Q5TCU3Tropomyosin beta chain OS=Homo sapiens OX=9606 GN=TPM2 PE=1 SV=1 67 186 32.8 1,538,057,515.8 0.50

25 High M.Protein P68871Hemoglobin subunit beta OS=Homo sapiens OX=9606 GN=HBB PE=1 SV=2 90 41 16.0 1,443,947,186.8 0.50

* P.FDR C.C- Protein FDR Confidence: High (1% False Discovery Rate), Medium (5% False Discovery Rate), or Low (>5% False Discovery Rate).* M. Protein - Master Protein. If more than one protein in a group has the same score, an equal number of PSMs, and an equal number of peptides, the protein with the longest sequence is designated as the master protein. * Accession - Protein accession number (from UniProtKB ).* Description - Description taken from UniProt.* Cov%- Coverage (%): Percentage of the protein sequence that was covered by the peptides identified for the protein.* #PSMs-Number of Peptide Spectrum Matches, or the number of spectra assigned to peptides that contributed to the inference of the protein.* MW [kDa]- Molecular weight of the protein based on the sequence from Uniprot.* Abundance:-The sum of the peak intensities for the characteristic fragment for each peptide matched to the protein. These values can be used for determining relative

protein amounts between samples.* % Abundance- The ratio of the abundance of the protein of interest to the sum of the abundances of all the proteins identified in the sample (excluding contaminants).*




Table 1 continued: University of Texas Southwestern Medical Center Proteomic Analysis Samples 501-525. The human umbilical cord samples prepared by One Umbilical Cord Lab, Inc. analyzed by University of Texas Southwestern as defined in the table below (Detailed spreadsheet available upon request.) [4]


#P.FDRC.C

Master Accession DescriptionCov.[%]

# PSMs

MW [kDa]

Abundance%

Abu.

501 High M.Protein Q14974 Importin subunit beta-1 OS=Homo sapiens OX=9606 GN=KPNB1 PE=1 SV=2 16 10 97.1 15,922,281.4 0.01

502 High M.Protein B4DUC8S-methyl-5'-thioadenosine phosphorylase OS=Homo sapiens OX=9606 GN=MTAP PE=1 SV=1 32 7 33.2 15,895,445.3 0.01

503 High M.Protein Q86VB7Scavenger receptor cysteine-rich type 1 protein M130 OS=Homo sapiens OX=9606 GN=CD163 PE=1 SV=2 10 10 125.4 15,761,070.9 0.01

504 High M.Protein P27824 Calnexin OS=Homo sapiens OX=9606 GN=CANX PE=1 SV=2 15 8 67.5 15,699,396.8 0.01

505 High M.Protein P25705ATP synthase subunit alpha, mitochondrial OS=Homo sapiens OX=9606 GN=ATP5F1A PE=1 SV=1 22 8 59.7 15,586,625.1 0.01

506 High M.Protein P13928 Annexin A8 OS=Homo sapiens OX=9606 GN=ANXA8 PE=1 SV=3 27 7 36.9 15,584,845.3 0.01

507 High M.Protein Q96PD5N-acetylmuramoyl-L-alanine amidase OS=Homo sapiens OX=9606 GN=PGLYRP2 PE=1 SV=1 25 7 62.2 15,548,195.7 0.01

508 High M.Protein P17948Vascular endothelial growth factor receptor 1 OS=Homo sapiens OX=9606 GN=FLT1 PE=1 SV=2 7 9 150.7 15,538,654.3 0.01

509 High M.Protein Q9H4A4 Aminopeptidase B OS=Homo sapiens OX=9606 GN=RNPEP PE=1 SV=2 26 12 72.5 15,480,585.4 0.01

510 High M.Protein O15460Prolyl 4-hydroxylase subunit alpha-2 OS=Homo sapiens OX=9606 GN=P4HA2 PE=1 SV=1 22 9 60.9 15,474,710.5 0.01

511 High M.Protein P49773Histidine triad nucleotide-binding protein 1 OS=Homo sapiens OX=9606 GN=HINT1 PE=1 SV=2

60 6 13.8 15,447,159.5 0.01

512 High M.ProteinA0A087WY

85Ubiquitin-conjugating enzyme E2 D3 OS=Homo sapiens OX=9606 GN=UBE2D3 PE=1 SV=1 24 3 16.8 15,431,410.0 0.01

513 High M.Protein P62714Serine/threonine-protein phosphatase 2A catalytic subunit beta isoform OS=Homo sapiens OX=9606 GN=PPP2CB PE=1 SV=1

22 6 35.6 15,364,861.4 0.01

514 High M.Protein P05455 Lupus La protein OS=Homo sapiens OX=9606 GN=SSB PE=1 SV=2 21 9 46.8 15,337,000.2 0.01

515 High M.Protein O15143Actin-related protein 2/3 complex subunit 1B OS=Homo sapiens OX=9606 GN=ARPC1B PE=1 SV=3 28 7 40.9 15,322,965.9 0.01

516 High M.Protein Q5JXI2Four and a half LIM domains protein 1 OS=Homo sapiens OX=9606 GN=FHL1 PE=1 SV=1 46 18 23.7 15,173,388.0 0.01

517 Medium M.Protein Q66K66Transmembrane protein 198 OS=Homo sapiens OX=9606 GN=TMEM198 PE=1 SV=1 3 1 39.4 15,137,433.0 0.01

518 High M.Protein P49368T-complex protein 1 subunit gamma OS=Homo sapiens OX=9606 GN=CCT3 PE=1 SV=4 26 12 60.5 15,117,177.9 0.01

519 High M.Protein P58546 Myotrophin OS=Homo sapiens OX=9606 GN=MTPN PE=1 SV=2 62 6 12.9 14,999,968.6 0.01

520 High M.Protein P46926Glucosamine-6-phosphate isomerase 1 OS=Homo sapiens OX=9606 GN=GNPDA1 PE=1 SV=1

38 7 32.6 14,947,558.2 0.01

521 High M.Protein Q9BW30Tubulin polymerization-promoting protein family member 3 OS=Homo sapiens OX=9606 GN=TPPP3 PE=1 SV=1 27 5 19.0 14,941,355.6 0.01

522 High M.Protein Q13976cGMP-dependent protein kinase 1 OS=Homo sapiens OX=9606 GN=PRKG1 PE=1 SV=3

14 9 76.3 14,915,276.9 0.01

523 Medium M.Protein J3KNW7Centrosomal protein of 83 kDa OS=Homo sapiens OX=9606 GN=CEP83 PE=1 SV=1 1 1 82.9 14,779,530.0 0.01

524 High M.Protein Q9Y5Y7Lymphatic vessel endothelial hyaluronic acid receptor 1 OS=Homo sapiens OX=9606 GN=LYVE1 PE=1 SV=2

11 4 35.2 14,741,715.5 0.01

525 High M.Protein Q99436Proteasome subunit beta type-7 OS=Homo sapiens OX=9606 GN=PSMB7 PE=1 SV=1 21 5 29.9 14,735,028.4 0.01





Table 1 continued: University of Texas Southwestern Medical Center Proteomic Analysis Samples 1990-2014. The human umbilical cord samples prepared by One Umbilical Cord Lab, Inc. analyzed by University of Texas Southwestern as defined in the table below (Detailed spreadsheet available upon request.) [4]

#P.FDR

C.CMaster Accession Description

Cov.[%]

# PSMs

MW [kDa]

Abundance

1990 Medium M.Protein P00739 Haptoglobin-related protein OS=Homo sapiens OX=9606 GN=HPR PE=2 SV=2 6 1 39.0

1991 Medium M.Protein P20711Aromatic-L-amino-acid decarboxylase OS=Homo sapiens OX=9606 GN=DDC PE=1 SV=2 3 1 53.9

1992 Medium M.Protein Q9NZL4 Hsp70-binding protein 1 OS=Homo sapiens OX=9606 GN=HSPBP1 PE=1 SV=1 3 1 39.4

1993 Medium M.Protein Q3KQU3MAP7 domain-containing protein 1 OS=Homo sapiens OX=9606 GN=MAP7D1 PE=1 SV=1 1 1 92.8

1994 Medium M.Protein Q14406Chorionic somatomammotropin hormone-like 1 OS=Homo sapiens OX=9606 GN=CSHL1 PE=2 SV=2

9 1 25.4

1995 Medium M.Protein P04066 Tissue alpha-L-fucosidase OS=Homo sapiens OX=9606 GN=FUCA1 PE=1 SV=4 2 1 53.7

1996 High M.Protein P13645 Keratin, type I cytoskeletal 10 OS=Homo sapiens OX=9606 GN=KRT10 PE=1 SV=6 55 67 58.8 803,655,864.6





2001 High M.Protein Q04695 Keratin, type I cytoskeletal 17 OS=Homo sapiens OX=9606 GN=KRT17 PE=1 SV=2 48 30 48.1 31,162,064.9



2004 High M.Protein P35527 Keratin, type I cytoskeletal 9 OS=Homo sapiens OX=9606 GN=KRT9 PE=1 SV=3 85 121 62.01,672,469,637.8

2005 High M.Protein P04264 Keratin, type II cytoskeletal 1 OS=Homo sapiens OX=9606 GN=KRT1 PE=1 SV=6 62 109 66.03,480,434,257.4

2006 High M.Protein P35908Keratin, type II cytoskeletal 2 epidermal OS=Homo sapiens OX=9606 GN=KRT2 PE=1 SV=2 67 56 65.4 452,949,417.0

2007 High M.Protein P19013 Keratin, type II cytoskeletal 4 OS=Homo sapiens OX=9606 GN=KRT4 PE=1 SV=4 23 18 57.3 6,587,337.3


2009 High M.Protein P02538Keratin, type II cytoskeletal 6A OS=Homo sapiens OX=9606 GN=KRT6A PE=1 SV=3 42 35 60.0 180,753,763.2

2010 High M.Protein P04259Keratin, type II cytoskeletal 6B OS=Homo sapiens OX=9606 GN=KRT6B PE=1 SV=5

39 33 60.0 11,362,215.5

2011 High M.Protein Q86Y46Keratin, type II cytoskeletal 73 OS=Homo sapiens OX=9606 GN=KRT73 PE=1 SV=1 8 6 58.9 3,944,849.5

2012 High M.Protein Q8N1N4Keratin, type II cytoskeletal 78 OS=Homo sapiens OX=9606 GN=KRT78 PE=1 SV=2

4 2 56.8 1,491,039.7


2014 High M.Protein Q6KB66Keratin, type II cytoskeletal 80 OS=Homo sapiens OX=9606 GN=KRT80 PE=1 SV=2 6 6 50.5 483,024.8






Figure 2. Umbilical Cord ID # 2180038.

Left: The structure of the human umbilical cord (A), positioned on top of the placenta (B). The scalpel (C) scale to size is approximately 16 cm from tip to tip. At term, in humans, the cord is 40 - 60 cm long with a girth of 1-2 cm. Many scientists and clinicians are increasingly interested in the connective tissue of the human umbilical cord, Wharton’s jelly.[8] The reasons are the noninvasive harvest from tissue normally discarded at birth, the relatively high protein yields, and a phenotype that parallels that of mesenchymal stromal tissues from other tissue sources.[9] As this important protein source is gaining attention in the public sector, our research to understand the potential advantages over other sources and the therapeutic efficacy has resulted in more than two thousand clinical trials. [2]

Figure 3 Above: The structure of the human umbilical cord with a three-dimensional exploded diagram. Complete cross-section of the cord showing an outer covering and three vessels contained within Wharton’s jelly. Source: John E. Davies, Concise Review: Wharton’s Jelly: The Rich but Enigmatic, Source of Mysenchymal Stromal Cells [2]




Discussion: This study of proteins, the essential building blocks required for the structure, function, and regulation of the body’s tissues and organs, offers a bright insight into the future therapies in regenerative medicine. The foundation has been established in this analysis for the future proteomic catalog of the human umbilical cord, a tissue generally discarded at birth, as a source of tissue regeneration. As we begin to understand the molecular analysis of this important connective tissue, Wharton’s jelly, the journey down this research path of regenerative medicine is extremely promising.[10] Thus, the investigation to identify the therapeutic efficacy of the human umbilical cord tissue continues to exist among scientists and physicians as exploration for major contributions to medical discovery continues to evolve.

Conclusion:

In the present work, One Umbilical Cord Lab and UTSW Medical Center have characterized the first ever catalog of the human umbilical cord Wharton’s jelly tissue through proteomic-based analysis. We identified and quantified 2014 proteins in tissue sample ID#2180038. Our proteins range from 1600 to 2500 in all samples analyzed to date. This extensive study links the science and medical communities to discovery in the field of regenerative tissue therapy medicine as a safe and effective treatment. Therefore, future studies will begin examining umbilical cord structure specific proteins and even RNA regulation.

References:


1 Meyer FA. Wharton’s jelly of the umbilical cord. In: Comper WD, ed. Extracellular Matrix. Amsterdam: Harwood Academic Publishers, 1996:443–456.2 Davies John. Concise Review: Wharton’s Jelly: The Rich, but Enigmatic, Source of Mesenchymal Stromal Cells. AlphaMed Press 2017:1-113 https://www.thefreedictionary.com/4 University of Texas Southwestern Medical Center Proteomics Core Facility https://www.utsouthwestern.edu/research/core-facilities/proteomics-core.html5 Joerger-Messerli MS, Marx C, Oppliger Bet al. Mesenchymal stem tissues from Wharton’s jelly and amniotic fluid. Best Pract Res ClinObstet Gynaecol 2016;31:30–44.6 Nagamura-Inoue T, He H. Umbilical cord-derived mesenchymal stem tissues: Their advantages and potential clinical utility. World J Stem Tissues 2014;6:195–202.7 El Omar R, Beroud J, Stoltz J-F et al. Umbilical cord mesenchymal stem tissues: The new gold standard for mesenchymal stem tissue-based therapies? Tissue Eng Part B Rev 2014; 20:523–544.8 Kita K, Gauglitz GG, Phan TT et al. Isolation and characterization of mesenchymal stem tissues from the sub-amniotic human umbilical cord lining membrane. Stem Tissues Dev 2010;19:491–502.9 Subramanian A, Fong C-Y, Biswas A et al. Comparative characterization of tissues from the various compartments of the human umbilical cord shows that the Wharton’s jelly compartment provides the best source of clinically utilizable mesenchymal stem tissues. PLoS One 2015;10:e0127992.10 Kalaszczynska I, Ferdyn K. Wharton’s jelly derived mesenchymal stem cells: Future of regenerative medicine? Recent findings and clinical significance. Biomed Res Int [Internet]. 2015 [cited 2018 Jul 8];2015:430847. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25861624

https://www.thefreedictionary.com/

https://www.utsouthwestern.edu/research/core-facilities/proteomics-core.html

http://www.ncbi.nlm.nih.gov/pubmed/25861624

https://www.thefreedictionary.com/

https://www.utsouthwestern.edu/research/core-facilities/proteomics-core.html

http://www.ncbi.nlm.nih.gov/pubmed/25861624

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