Suitability of milk as a storage media used during transportation



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Hi Lorna.
In preparation for our Skype teleconference tomorrow, I have made a short list of items that hopefully can be covered during the teleconference.


  • Your takeup experience overseas

(FANTASTIC! )

  • How collected/transported – milk

We supply two tooth collection tubes with each kit. The customer provides their own off the shelf pasteurized cow’s milk. Commercially available cow milk is a highly regulated product in most industrialized countries. The quality, sterility, and consistency are very good. Milk also has a strong anti-growth effect on microbial contaminants from the mouth while helping to preserve the viability of mammalian cells. We need to receive the sample within 72 hours for the best results and 24 hours is more normal and expected.

  • Research material relating to cells collected this way

Suitability of milk as a storage media used during transportation (Scientific papers and references)

American association of endodontist

November 1997, Volume 23, Number 11

http://www.aae.org/aae-cms/Templates/internal_heading.aspx?NRMODE=Published&NRORIGINALURL=%2fjoe%

Comparison of Various Transport Media on Human Periodontal Ligament Cell Viability
Brian D. Olson, DMD, Jason M. Mailhot, DMD, MS, Ronald W. Anderson, DDS, MS, George S. Schuster, DDS, MS, PhD, and R. Norman Weller, DMD, MS

The purpose of this study was to determine the ability of various solutions to maintain human periodontal ligament cell (PDL) viability in vitro. PDL cells were obtained from extracted third molars and premolars of healthy individuals. These cells were placed into 24-well culture plates containing milk, Save-A-Tooth, Save-A-Tooth supplemented with platelet-derived growth factor-BB (PDGF), or Gatorade at a concentration of 80,000/well. Cells left dry served as negative controls, and cells placed in Eagles' Minimal Essential Medium served as positive controls. At 1, 2, 4, 8, and 12 h, cell viability was evaluated using an MTS assay and an ELISA plate reader to determine optical density. ANOVA and Student-Newman-Keuls tests indicated that milk and Save-A-Tooth with PDGF are suitable as transport medium for avulsed teeth and that the addition of PDGF to Save-A-Tooth may enhance its ability to maintain PDL cell viability. They also suggests that Gatorade would be unsuitable as a transport medium.


Extra-Alveolar Storage Media For Tooth Autotransplants And Replants

http://www.ispub.com/ostia/index.php?xmlFilePath=journals/ijds/vol2n2/alveolar.xml#e9


Abstract

The maintenance of the vitality of the cells of the periodontal ligament and cementum is essential for the long-term success of a transplant or replant. The tooth is surgically transferred from its initial position, without traumatizing the cells of the periodontal ligaments and cementum, into a new socket. An appropriate storage medium should maintain or improve the vitality of the cells during the extra-alveolar period; when the new socket is being prepared or the tooth being transported for replantation after an avulsion.


Storage media proposed in the literature include Hank's Balanced Salt Solution (HBSS), patient's own serum, isotonic saline, tap water, saliva and pasteurized milk. The most favoured ones are HBSS, patient's own serum, Eagle's culture medium, pasteurized milk and isotonic saline.

Long shelf-life milk, which has the advantage of not requiring refrigeration, is as effective a storage medium for avulsed teeth as regular pasteurized milk and more effective than Save-A-Tooth medium ( 27 ). Similarly, in their study to determine the efficacy of several milk substitutes: reconstituted powdered milk, evaporated milk or one of two baby formulas: Similac or Enfamil; compared to whole milk, in maintaining the viability of human PDL cells on avulsed teeth, Pearson et al ( 28 ) reported that Enfamil, which is supplied in powdered that does not require special storage and has a shelf-life of 18months, is a more effective storage medium for avulsed teeth than pasteurized or whole milk for at least 4 hours.

However in another study to determine the periodontal ligament cell vitality from extracted teeth stored in saline or milk using fluorescein dictate as a staining medium, Patel et al ( 9 ) found that there was no statistically significant difference in the number of viable cells on the root surfaces of teeth after 2 hours of storage in either milk or saline.

Newly extracted teeth from monkeys were stored in saline, milk or saliva for 1 to 3 hours by Blomlof et al ( 29 ). Frozen sections were made and the vitality of the periodontal ligaments determined histochemically. Cells seemed to survive better in milk than saliva and saline. The reason for this, according to the authors, may be that milk contains important nutritional substances such as amino acids, carbohydrates and vitamins. Also, the commercially available milk is pasteurized, which may inactivate enzymes that are potentially harmful to the periodontal ligament. Saliva on the other hand contains potentially harmful substances such as enzymes, bacteria and their products.

Huang et al ( 30 ) exposed cultured PDL cells from healthy extracted human teeth to milk, Alcon Optic – Free contact lens solution, K- Mart contact lens solution, saline and Hank's balanced salt solution (HBSS). The appearance and rate off loss of the cells from the culture dishes were recorded over time at both room temperature (20 degrees Centigrade) and 4 degrees Centigrade. The results indicated that saline was superior to either of the contact lens solutions in its ability to maintain the vitality of the PDL cells. Milk at 4 degrees provided good short-term viability. The study supports milk as a good short-term storage medium for maintaining the viability of PDL cells in vitro.

Layug et al ( 31 ) proposed that milk packed in ice seems to be the best alternative amongst; Modified Eagle's Medium, HBSS, saline and saliva, for the temporary storage of avulsed teeth due to its wide availability and the minimal detrimental effect it has on the PDL cells.

The tooth storage media that are therefore mostly favoured in the literature include: HBSS, patient's own serum, Eagle's culture medium, pasteurized milk and isotonic (normal) saline. HBSS significantly preserved the viability of the PDL cells during the crucial extra-alveolar period ( 33 , 34 , 35 , 36 ). Serum also maintained the vitality of the periodontal membrane during the extra-alveolar period ( 15 ) while Eagle's medium allowed the proliferation of vital parts of the periodontium to cover area of root surface with denuded or necrotic periodontal membrane ( 21 , 22 , 23 ) Pasteurized milk contains important nutritional substances such as amino acids, carbohydrates and vitamins, which are useful to the periodontium ( 26 , 29 , 30 , 38 ) while isotonic saline also maintained the vitality of periodontal membrane during the critical extra-alveolar period ( 17 , 18 , 19 ).



References

1. Morse D.R. PART ONE: Historical review J. Oral Implantol ,(2): 176-192, 1977.

2. Andreasen JO, Hjorting-Hansen E. Replantation of teeth I. Radiographic and clinical study of 110 human teeth replanted after accidental loss Acta Odontol. Scandinavia, 24: 263-286, 1966.

3. Moss JP -Autogenous transplantation of maxillary canines. J. Oral Surg. 26(1): 775-783, 1968.

4. Nordenram A. Autotransplantation of teeth. A clinical investigation. Brit. J. Oral Surg; 7: 188- 195, 1970.

5. Andreason JO - The effect of extra-alveolar period and storage media upon periodontal and pulpal healing after replantation of mature permanent in monkeys. Int. J. Oral Surg; 10: 43-53, 1981.

6. Moss JP - The indication for the transplantation of maxillary canines in the light of 100 cases. Brit. J. Oral Surg; 12: 268-274,1975.

7. Andreasen JO. Paulsen HU. Yu-z. et al - A long-term study. Part I. Surgical procedures and standardized techniques for monitoring healing. Eur. J. Ortho; 12 (1): 3-13,1990.

8. Andreasen JO. Hjorting-Hansen E; Jolst: A clinical and radiographic study of 76 autotransplanted third molars. Scandinavian J. Dent Res; 78: 512-523, 1970.

9. Patel S., Dumsha TC., Sydiskis RJ. Determining periodontal ligament (PDL) cell vitality from exarticulated teeth stored in saline, or milk using fluorescein diacetate Int. Endo. J; 27:1-5, 1994.

10. Fagade OO. Tooth Transplantation - A revival article. Afr. J. Med Pharm Sci; 1:28-32, 1997.

11. Loe H, Waerhaug J. Experimental replantation of teeth in dogs and monkeys Arch. Oral Biol.;3: 176-184, 1961.

12. Blomlof L., Andersson L., Lindskog S., Hedstrom KG., Hammarstrom L. Periodontal healing of replanted monkey teeth prevented from drying Acta Odontol. Scandinavia; 4(2):117-123, 1983.

13. Fagade O.O., Gillbe G.V, Wastell D.G. Radiographic pattern of root resorption in autotransplanted maxillary canines. J. Dent; 16:80-84, 1988.

14. Fagade O.O., Effect of surgical details on the incidence of root resorption on auto-transported maxillary canines. A retrospective study. Nig. Dent. J; 11(2): 8-12, 1997.

15. Thonner K.E. Autogenous transplantation of unerupted maxillary canines. A clinical and histological investigation over five years. The Dent Practitioner ; 21(7); 251-257, 1971.

16. Martin MP, Pileggi R. A quantitative analysis of Propolis: a promising new storage medium following avulsion. Dent Traumatol; 20(2): 85-89,2004.

17. Altonen M., Haavikko K, Malmstrom M. Evaluation of autotransplantation of completely developed maxillary canines. Int. J. Oral Surg; 7: 434-441, 1978.

18. Burley MA, Grabb HS. Replantation of teeth Brit. Dent J. 108(5): 190-193, 1960.

19. Andreasen JO. Analysis of topography of surface and inflammatory root resorption after replantations of mature permanent incisors in monkeys. Swedish Dent. J. 4: 135-144,1980.

20. Nasjlet CE.,Caffese RG., Castelli WA. Replantation of mature teeth without endodontic in monkeys J.Dent. Res. 57: 650-658, 1978.

21. Andreasen JO, Reinholdt JI, Dybdahl R., Soder PO., Otteskog P. Periodontal and pulpal healing of monkey incisors preserved in tissue culture before replantation Int. J. Oral Surg. 7: 104:112, 1978.

22. Litwin J, Lundquist, Soder PO. Studies on long-term maintenance of teeth and viable associated cells in vitro. Scandinavian J.Deut. Res. 79: 536-539, 1971.

23. Thomsson M., Blomlof L., Ottenskog PO, Hammarstrom L. A clinical and radiographic evaluation of cultivated and autotransplanted human teeth. Int. J. Oral Surg. 13(3): 211-220, 1984.

24. Pohl Y, Tekin U. Boll M, Filippi A, Kirschner H. Investigations on a cell culture medium for storage and transportation of avulsed teeth. Aust Endod J. 25(2): 70-75, 1999.

25. Pongsiri S, Schiegel D. Zimmermann M. Survival rate of periodontal ligament cells after extraoral storage in different media. Duch Z. Mund Kiefer Gesichtschir. 14(5): 364-368,1990.

26. Blomlof L., Otteskog P. Vitality of human periodontal ligament cells after storage in milk or saliva. Scandinavian J. Dent. Res. 88: 436-440, 1980.

27. Marino TG, West LA, Liewehr FR, et al. Determination of periodontal ligament cell viability in long shelf-life milk. J. Endod. 26(12): 699-702, 2000.

28. Pearson RM, Liewehr FR, WestLA, et al. Human periodontal ligament cell viability in milk and milk substitutes. J Endod. 29(3): 184-186, 2003.

29. Blomlof L., Lindskog S., Hedstrom KG. Hammarstrom L. Vitality of periodontal ligament cells after storage of monkey teeth in milk or saliva. Scandinavian J. Dent. Res. 88: 441-445, 1980.

30. Huang SC, Remeikis NA, Daniel JC. Effects of long-term exposure of human periodontal ligament cells to milk and other solutions. J Endod. 22(1): 30-33,1996.

31. Layug ML, Barrett FJ, KennyDJ. Interim storage of avulsed permanent teeth. J Can Dent Assoc. 64(5): 357-363, 365-369, 1998.

32. Lekic P, Kenny D. Moe HK et al. Relationship of clonogenic capacity to plating efficiency and vital dye staining of human periodontal ligament cells: implication for tooth replantation. J Periodontal Res. 31(4): 294-300, 1996.

33. Ashkenazi M, Sarnat H, Keila S. In vitro viability, mitogenicity and clonogenic capacity of periodontal ligament cells after storage in six different media. Endod Dent Traumatol 15(4) 149-156, 1999.

34. Ashkenazi M, Maronni M, Sarnat H. In vitro viability, mitogenicity and clonogenic capacity of periodontal ligament cells after storage in four media at room temperature. Endod Dent Traumatol. 16(2): 63-70, 2000.

35. Ashkenazi M, Marouni M, Sarnat H. In vitro viability, mitogenicity and clonogenic capacities of periodontal ligament fibroblasts after storage in four media supplemented with growth factors. Dent Traumatol. 17(1): 27-35, 2001.

36. Sigalas F, Regan JD, Kramer PR, et al. Survival of human periodontal ligament cells in media proposed for transport of avulsed teeth. Dent Traumatol. 20(1): 21-28, 2004.

37. Schwartz O, Andreasen FM, Andreasen JO. Effects of temperature, storage time and media on periodontal and pulpal healing after replantation of incisors in monkeys. Dent Traumatol. 18(4): 190-185, 2002.



38. Blomlof L, Lindskog S, Hammarstrom L. Effect of storage in media with different ion strengths and osmolalities on human periodontal ligament cells. Scandinavian J. Dent Res. 89: 180-187, 1980.


(I would not want to discuss how many cells we obtain from a tooth or exactly how many doublings we have tested without an NDA)
I will assume that this question relates specifically to MSC’s from teeth because there is such an abundance of publications proving the expansion potential of MSC’s from bone marrow.
There are a number of publications that list how many population doublings were obtained from MSC’s isolated from teeth. The published numbers range from 80 doublings to 120 doublings depending on the lab and the exact culture conditions used.  Here is a chart to demonstrate how population doublings relates to total cell number.

Cellular Expansion of MSC from Teeth

Total Number of MSC's Isolated

Number of Cell Divisions

Total Number of Expanded Cells

1

1

2




2

4




3

8




4

16




5

32




6

64




7

128




8

256




9

512




10

1024




11

2048




12

4096




13

8192




14

16384




15

32768




16

65536




17

131072




18

262144




19

524288




20

1048576




21

2097152




22

4194304




23

8388608




24

16777216




25

33554432




26

67108864




27

134217728




28

268435456




29

536870912




30

1073741824




31

2147483648




32

4294967296




33

8589934592




34

17179869184




35

34359738368




36

68719476736




37

1.37439E+11




38

2.74878E+11




39

5.49756E+11




40

1.09951E+12




41

2.19902E+12




42

4.39805E+12




43

8.79609E+12




44

1.75922E+13




45

3.51844E+13




46

7.03687E+13




47

1.40737E+14




48

2.81475E+14




49

5.6295E+14




50

1.1259E+15




51

2.2518E+15




52

4.5036E+15




53

9.0072E+15




54

1.80144E+16




55

3.60288E+16




56

7.20576E+16




57

1.44115E+17




58

2.8823E+17




59

5.76461E+17




60

1.15292E+18




61

2.30584E+18




62

4.61169E+18




63

9.22337E+18




64

1.84467E+19




65

3.68935E+19




66

7.3787E+19




67

1.47574E+20




68

2.95148E+20




69

5.90296E+20




70

1.18059E+21




71

2.36118E+21




72

4.72237E+21




73

9.44473E+21




74

1.88895E+22




75

3.77789E+22




76

7.55579E+22




77

1.51116E+23




78

3.02231E+23




79

6.04463E+23




80

1.20893E+24




81

2.41785E+24




82

4.8357E+24




83

9.67141E+24




84

1.93428E+25




85

3.86856E+25




86

7.73713E+25




87

1.54743E+26




88

3.09485E+26




89

6.1897E+26




90

1.23794E+27




91

2.47588E+27




92

4.95176E+27




93

9.90352E+27




94

1.9807E+28




95

3.96141E+28




96

7.92282E+28




97

1.58456E+29




98

3.16913E+29




99

6.33825E+29




100

1.26765E+30

A couple of very important things to remember when looking at this excel data.

  1. All numbers shown are based on the isolation of a single cell from a tooth sample (shown in the first box).  We get many cells but I used a single cell for these calculations to demonstrate the point better.

  2. I only expanded the cells for 100 doublings in this example which is a safe middle point of the published papers.

  3. We have functionally tested BioEDEN material in this type of experiment to prove that our material can expand this many times without loss of functionality and it does.

  4. A typical cell therapy procedure may use about 200 million (2.0x108).  In our example here we would reach that number on day 28 of culture when starting from a single cell.  If we were to thaw a typical customer sample and place it in culture it would generate this same number on day 7 of culture.




  • Information re use of cells clinically

Selected Publications on Therapy Using Stem Cells from Teeth
Peer-Reviewed Publications using Dental Pulp Stem Cells in Animals and Humans (in vivo)
Bone Formation
Stem cells from dental pulp have been shown to have the ability to differentiate into osteoblasts. Studies have shown that dental pulp stem cells are a promising tool for bone generation. Stem cells from teeth have been expanded, differentiated, and implanted into animal models and have repaired bone defects. Stem cells from dental pulp may one day be used to treat human bone disorders, like osteoporosis, bone injury, and bone deformation.
Human mandible bone defect repair by the grafting of dental pulp stem/progenitor cells and collagen sponge biocomplexes.

d'Aquino R, De Rosa A, Lanza V, Tirino V, Laino L, Graziano A, Desiderio V, Laino G, Papaccio G.

Eur Cell Mater. 2009 Nov 12;18:75-83. PMID: 19908196

http://www.ncbi.nlm.nih.gov/pubmed/19908196
Stem cells from deciduous tooth repair mandibular defect in swine.

Zheng Y, Liu Y, Zhang CM, Zhang HY, Li WH, Shi S, Le AD, Wang SL.

J Dent Res. 2009 Mar;88(3):249-54. PMID: 19329459

http://www.ncbi.nlm.nih.gov/pubmed/19329459
SHED repair critical-size calvarial defects in mice.

Seo BM, Sonoyama W, Yamaza T, Coppe C, Kikuiri T, Akiyama K, Lee JS, Shi S.

Oral Dis. 2008 Jul;14(5):428-34. PMID: 18938268

http://www.ncbi.nlm.nih.gov/pubmed/18938268
Dental pulp stem cells: a promising tool for bone regeneration.

d'Aquino R, Papaccio G, Laino G, Graziano A.

Stem Cell Rev. 2008 Spring;4(1):21-6. PMID: 18300003

http://www.ncbi.nlm.nih.gov/pubmed/18300003
In vivo evaluation of human dental pulp stem cells differentiated towards multiple lineages.

Zhang W, Walboomers XF, Van Kuppevelt TH, Daamen WF, Van Damme PA, Bian Z, Jansen JA.

J Tissue Eng Regen Med. 2008 Mar-Apr;2(2-3):117-25. PMID: 18338838

http://www.ncbi.nlm.nih.gov/pubmed/18338838
Reconstruction of large cranial defects in nonimmunosuppressed experimental design with human dental pulp stem cells.

de Mendonça Costa A, Bueno DF, Martins MT, Kerkis I, Kerkis A, Fanganiello RD, Cerruti H, Alonso N, Passos-Bueno MR.

J Craniofac Surg. 2008 Jan;19(1):204-10. PMID: 18216690

http://www.ncbi.nlm.nih.gov/pubmed/18216690
Mesenchymal progenitor cells in adult human dental pulp and their ability to form bone when transplanted into immunocompromised mice.

Otaki S, Ueshima S, Shiraishi K, Sugiyama K, Hamada S, Yorimoto M, Matsuo O.

Cell Biol Int. 2007 Oct;31(10):1191-7. Epub 2007 Apr 14. PMID: 17524678

http://www.ncbi.nlm.nih.gov/pubmed/17524678

Cornea
Dental pulp stem cells have been implanted in an animal model to reconstruct cornea of the eye. This is promising for the development of human cornea reconstruction therapies to treat damage due to limbal stem cell deficiencies, chemical injury of the eye, dry eye, and ageing.
Corneal reconstruction with tissue-engineered cell sheets composed of human immature dental pulp stem cells.

Gomes JA, Geraldes Monteiro B, Melo GB, Smith RL, Cavenaghi Pereira da Silva M, Lizier NF, Kerkis A, Cerruti H, Kerkis I.

Invest Ophthalmol Vis Sci. 2010 Mar;51(3):1408-14. Epub 2009 Nov 5. PMID: 19892864

http://www.ncbi.nlm.nih.gov/pubmed/19892864
Fat
Dental pulp stem cells have been shown to differentiate into adipocytes – fat cells. While most people are trying to get rid of fat from their bodies, fat is a useful tissue in reconstructive surgery after mastectomy and cosmetic surgery.
In vivo evaluation of human dental pulp stem cells differentiated towards multiple lineages.

Zhang W, Walboomers XF, Van Kuppevelt TH, Daamen WF, Van Damme PA, Bian Z, Jansen JA.

J Tissue Eng Regen Med. 2008 Mar-Apr;2(2-3):117-25. PMID: 18338838

http://www.ncbi.nlm.nih.gov/pubmed/18338838
Muscle
Dental pulp stem cells have been shown to differentiate into myocytes – muscle cells. This is exciting because it implicates the possibility of dental pulp stem cells to be used to treat muscle injury and diseases like muscular dystrophy.
Early transplantation of human immature dental pulp stem cells from baby teeth to golden retriever muscular dystrophy (GRMD) dogs: Local or systemic?

Kerkis I, Ambrosio CE, Kerkis A, Martins DS, Zucconi E, Fonseca SA, Cabral RM, Maranduba CM, Gaiad TP, Morini AC, Vieira NM, Brolio MP, Sant'Anna OA, Miglino MA, Zatz M.

J Transl Med. 2008 Jul 3;6:35. PMID: 18598348

http://www.ncbi.nlm.nih.gov/pubmed/18598348
In vivo evaluation of human dental pulp stem cells differentiated towards multiple lineages.

Zhang W, Walboomers XF, Van Kuppevelt TH, Daamen WF, Van Damme PA, Bian Z, Jansen JA.

J Tissue Eng Regen Med. 2008 Mar-Apr;2(2-3):117-25. PMID: 18338838

http://www.ncbi.nlm.nih.gov/pubmed/18338838
Nerve Regeneration
Dental pulp stem cells have been shown to differentiate into functional neurons in animal models. Some day dental pulp stem cells may be used to treat human paralysis due to nerve injury or disease and may even be used treat nerve diseases like multiple sclerosis.
Integration of neuronally predifferentiated human dental pulp stem cells into rat brain in vivo.

Király M, Kádár K, Horváthy DB, Nardai P, Rácz GZ, Lacza Z, Varga G, Gerber G.

Neurochem Int. 2011 Jan 8. [Epub ahead of print]. PMID: 21219952

http://www.ncbi.nlm.nih.gov/pubmed/21219952
Implanted Adult Human Dental Pulp Stem Cells Induce Endogenous Axon Guidance.

Arthur A, Shi S, Zannettino AC, Fujii N, Gronthos S, Koblar SA.

Stem Cells. 2009 Sep;27(9):2229-37. PMID: 19544412

http://www.ncbi.nlm.nih.gov/pubmed/19544412
Putative Dental Pulp Derived Stem/Stromal Cells Promote Proliferation and Differentiation of Endogenous Neural Cells in the Hippocampus of Mice.

Huang AH, Snyder BR, Cheng PH, Chan AW.

Stem Cells. 2008 Aug 7. PMID: 18687995

http://www.ncbi.nlm.nih.gov/pubmed/18687995
Adult human dental pulp stem cells differentiate toward functionally active neurons under appropriate environmental cues.

Arthur A, Rychkov G, Shi S, Koblar SA, Gronthos S.

Stem Cells. 2008 Jul;26(7):1787-95. PMID: 18499892

http://www.ncbi.nlm.nih.gov/pubmed/18499892
Tooth
Stem cells from dental pulp may one day be used to engineer whole, implantable teeth to replace teeth that are lost due to injury or disease.
Dental Stem Cell Therapy with Calcium Hydroxide in Dental Pulp Capping.

Ji YM, Jeon SH, Park JY, Chung JH, Choung YH, Choung PH.

Tissue Eng Part A. 2010 Feb 17. PMID: 20055661

http://www.ncbi.nlm.nih.gov/pubmed/20055661
Dental pulp tissue engineering with stem cells from exfoliated deciduous teeth.

Cordeiro MM, Dong Z, Kaneko T, Zhang Z, Miyazawa M, Shi S, Smith AJ, Nör JE.

J Endod. 2008 Aug;34(8):962-9. PMID: 18634928

http://www.ncbi.nlm.nih.gov/pubmed/18634928
In vivo evaluation of human dental pulp stem cells differentiated towards multiple lineages.

Zhang W, Walboomers XF, Van Kuppevelt TH, Daamen WF, Van Damme PA, Bian Z, Jansen JA.

J Tissue Eng Regen Med. 2008 Mar-Apr;2(2-3):117-25. PMID: 18338838

http://www.ncbi.nlm.nih.gov/pubmed/18338838
Diabetes (Type 1)
Insulin secreting cells malfunction or are destroyed in patients with diabetes. Stem cells from teeth have been shown to differentiate into insulin secreting cells. Cells from teeth haven’t been used to treat diabetes in animals yet, however they nearly identical in form and function to mesenchymal stem cells from bone marrow that have been shown to revert type 1 diabetes in mice.
Differentiation of Dental Pulp Stem Cells Into Islet Like Aggregates.

Govindasamy V, Ronald VS, Abdullah AN, Ganesan Nathan KR, Ab Aziz ZA, Abdullah M, Musa S, Abu Kasim NH, Bhonde RR.

J Dent Res. 2011 Feb 18. [Epub ahead of print]. PMID: 21335539

http://www.ncbi.nlm.nih.gov/pubmed/21335539

**This research was performed using dental pulp stem cells in vitro (in a dish).


Systemic administration of multipotent mesenchymal stromal cells reverts hyperglycemia and prevents nephropathy in type 1 diabetic mice.

Ezquer FE, Ezquer ME, Parrau DB, Carpio D, Yañez AJ, Conget PA.

Biol Blood Marrow Transplant. 2008 Jun;14(6):631-40. PMID: 18489988

http://www.ncbi.nlm.nih.gov/pubmed/18489988

**This research was performed using bone marrow MSCs, which function the same as dental pulp stem cells in other studies.


Mesenchymal stem cells: Stem cell therapy perspectives for type 1 diabetes.

Vija L, Farge D, Gautier J-F, Vexiau P, Dumitrache C, Bourgarit A, Verrecchia F, Larghero J.

Diabetes and Metabolism. 2009 Apr;35(2):85-93. PMID: 19230736

http://www.ncbi.nlm.nih.gov/pubmed/19230736

**This research was performed using bone marrow MSCs, which function the same as dental pulp stem cells in other studies.


Myocardial Infarction (Heart Attack)
Animals have been treated with human dental pulp stem cells to treat heart injury caused by a heart attack.
Human dental pulp stem cells improve left ventricular function, induce angiogenesis, and reduce infarct size in rats with acute myocardial infarction.

Gandia C, Armiñan A, García-Verdugo JM, Lledó E, Ruiz A, Miñana MD, Sanchez-Torrijos J, Payá R, Mirabet V, Carbonell-Uberos F, Llop M, Montero JA, Sepúlveda P.

Stem Cells. 2008 Mar;26(3):638-45. PMID: 18079433

http://www.ncbi.nlm.nih.gov/pubmed/18079433
Parkinson’s Disease
Dental pulp stem cells can differentiate into functional neurons and have been used in animals to reduce the symptoms of Parkinson’s Disease, a disease of the central nervous system.
Human dental pulp stem cells protect mouse dopaminergic neurons against MPP(+) or rotenone.

Nesti C, Pardini C, Barachini S, D'Alessandro D, Siciliano G, Murri L, Petrini M, Vaglini F.

Brain Res. 2011 Jan 7;1367:94-102. Epub 2010 Sep 18. PMID: 20854799

http://www.ncbi.nlm.nih.gov/pubmed/20854799
Reconstruction of large cranial defects in nonimmunosuppressed experimental design with human dental pulp stem cells.

de Mendonça Costa A, Bueno DF, Martins MT, Kerkis I, Kerkis A, Fanganiello RD, Cerruti H, Alonso N, Passos-Bueno MR.

J Craniofac Surg. 2008 Jan;19(1):204-10. PMID: 18216690

http://www.ncbi.nlm.nih.gov/pubmed/18216690
Stem Cells from Human Exfoliated Deciduous Teeth Can Differentiate into Dopaminergic

Neuron-like Cells.

Wang J, Wang X, Sun Z, Wang X, Yang H, Shi S, Wang S.

Stem Cells Dev. 2010 Sep;19(9):1375-83. PMID: 20131979

http://www.ncbi.nlm.nih.gov/pubmed/20131979
Wound Healing
Dental pulp stem cells could be used to heal wounds due to injury, surgery, infection, and disease.
Human Deciduous Teeth Dental Pulp Cells With Basic Fibroblast Growth Factor Enhance Wound Healing of Skin Defect.

Nishino Y, Ebisawa K, Yamada Y, Okabe K, Kamei Y, Ueda M.

J Craniofac Surg. 2011 Mar 9. [Epub ahead of print]. PMID: 21403563

http://www.ncbi.nlm.nih.gov/pubmed/21403563
Stem cells from human exfoliated deciduous teeth (SHED) enhance wound healing and the possibility of novel cell therapy.

Nishino Y, Yamada Y, Ebisawa K, Nakamura S, Okabe K, Umemura E, Hara K, Ueda M.

Cytotherapy. 2011 Feb 22. [Epub ahead of print]. PMID: 21341975

http://www.ncbi.nlm.nih.gov/pubmed/21341975
Ischemia/Angiogenesis/Vasculogenesis
Dental pulp stem cells can be used to create new blood vessels. They could be used in the treatment of heart damage from heart attack, and to grow blood vessels to give blood a route to regenerated tissue or tissue that has lost its blood supply.
A novel stem cell source for vasculogenesis in ischemia: subfraction of side population cells from dental pulp.

Iohara K, Zheng L, Wake H, Ito M, Nabekura J, Wakita H, Nakamura H, Into T, Matsushita K, Nakashima M.

Stem Cells. 2008 Sep;26(9):2408-18. Epub 2008 Jun 26.. PMID: 18583536

http://www.ncbi.nlm.nih.gov/pubmed/18583536
Liver Disease
Dental pulp stem cells may one day be used to treat liver disease caused by infection and inflammation (hepatitis), congenital liver disease, and alcoholism.
Multipotent cells from the human third molar: feasibility of cell-based therapy for liver disease.

Ikeda E, Yagi K, Kojima M, Yagyuu T, Ohshima A, Sobajima S, Tadokoro M, Katsube Y, Isoda K, Kondoh M, Kawase M, Go MJ, Adachi H, Yokota Y, Kirita T, Ohgushi H.

Differentiation. 2008 May;76(5):495-505. Epub 2007 Dec 17. PMID: 18093227

http://www.ncbi.nlm.nih.gov/pubmed/18093227
Web Publications Using Mesenchymal Stem Cells from Bone Marrow in Humans
A woman’s own MSC’s were used to grow a transplant trachea.

1st Trachea Transplant From Stem Cells

Doctors Use Patient's Stem Cells to Prepare Donor's Trachea

WebMD Health News; By Miranda Hitti



http://www.webmd.com/news/20081119/1st-trachea-transplant-from-stem-cells
MSC’s are used to grow replacement cartilage for damaged shoulders in humans.

Adult Stem Cells for Shoulder Injuries

On Target



http://blog.targethealth.com/?p=3802
MSC’s are used for difficult wound healing and skin growth in human patients.

New Study Using Combination of Bioengineered Skin and Stem Cells Shows Promise in Treatment of Non-Healing Wounds

By: PR Newswire



http://uk.sys-con.com/node/866081



  • What processing involves – how long

The process can take as long as 21 days however it typically occurs in less than 14 days.


  • Regulator accreditation - TGA?

The TGA reviewed the BioEDEN process in 2008 when we were previously looking at opening of operations in Australia. The TGA gave their approval and said that they couldn’t identify any problem areas between our process and existing regulations.
We currently have approval from both the HTA in the UK and the FDA in the USA.


  • Equipment required

(I would not want to discuss equipment requirements without an NDA)

The BioEDEN process does require specialized equipment for the isolation, culture, and testing of human Mesenchymal stem cells. There would be very little overlap between this equipment and the equipment used for the isolation and storage of stem cells from cord blood.





  • Storage (vials?)

Yes, the material is stored in a non-expanded state in the vapour phase of liquid nitrogen.


  • Service price -NA

  • Timeframe -NA

Obviously you will have other matters you would also like to raise.


Other considerations:

        1. Control of lab processes. We will require oversight control of the processing facility to insure that the BioEDEN process is not being compromised or modified without our consent.

        2. Use of our BLMS. This is required for us to properly audit both the financial and scientific process. I suspect they will have a knee jerk problem with this because it would require an IT infrastructure that is not currently in place as well as significant training of employees.

        3. Blood sample acquisition for infectious disease testing. This is generally not an issue with cord blood because it is obtained at the time of birth from existing material. This does not apply to our business model and we need to identify potential problems in advance.


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