TCS - PGI SYMPOSIUM PART 2

1.    CD 38+ is the characterisation of Pluripotent stem cells. All cells have this positive.

2.    If CD 34+ then it is committed stem cells. 

MESENCHYMAL STEM CELLS FROM THE UMBLICAL CORD: A USEFUL SOURCE

Stem cells have self-renewal and differentiation capacity.

Totipotent cells-	Early embryo
Pluripotent cells	Blastocyst
Multipotent stem cells	Adult stem cells

1.     Embryonic stem cells- objectionable

2.     Foetal stem cells- ok but still some problem

3.     Mesenchymal stem cells- can renew into neural tissue also?

4.     MSC derived from old age people have reduced capacity of proliferation.

5.     HYPOTHESIS PROPOSED: UNIVERSAL STEM CELLS BY ALLOTRANSPLANTATION WITHOUT REQUIREMENT OF IMMUNO SUPRESSION.

6.     MSC are hypo immunogenic and also alter the immune response and modulate the T cells phenotype

Having low level of MHC II and lack of MHC I

MSC downregulate the T cell response.

These immune regulatory property encourage them to be used in lot of AUTOIMMUNE DISORDER and can be used for allogenic transplants.

7.     MSC has an enormous proliferating capacity and this is very important in making them enlarge very fast.

8.     Sources of MSC

Umbilical cord matrix, Umbilical cord blood, Placenta, Amniotic fluid (Neonatal MSC)

Other sources Bone marrow, Adipose tissue. (Adult MSC)

9.     Neonatal MSC are useful as age related changes which occur in the adult MSC will not occur over here.

10.  Plasticity, homing are some of the property required for both Neonatal as well as Adult stem cells.

11.  Wharton’s jelly is the source of the MSC in the umbilical cord.

12.  Explants method

Take the umbilical cord – Mice into small pieces

 Keep in the plate, the MSC will adhere to the basement of the plate and will grow         enormously.

13.  Another is Digestion method

14.  MSC also have safety issue and but some study research said that does not have any malignant transformation potential.

15.  There is an ocean full of pearls and we need to search the pearls for the good.

2 R’S OF MESENCHYMAL STEM CELLS-REPAIR AND REGENERATION

1.     E. Donnnall Thomas 1990

2.     Yamanaka -2012 Noble prize

3.     Artificial trachea- lancet 20087

4.     Artificial urethra-2011

5.     MSC are used in more than 76% of the trial.

6.     Earlier paracrine factor was thought to be responsible for causing proliferation of the stem cell injected area.

Transdifferentiate

Exosomes are released from the MSC- they have some receptor will go and add to the recipient cells and help them to regenerate.

7.     Dendritic derived Exosomes in severe cancer- Trial going on.

8.     MSC have many healthy mitochondria which get transferred from the MSC to the dying cells. This is documented.

9.     5 azacytidine is the commonly used for the characterisation of MSC into the cardiac cells.

10.  TGF beta also characterise the MSC into cardiac cells.

11.  FGF-2 helps in transformation to neural tissue. Something else are also there.

12.  Take a nerve cut it and then connect the cut by keeping a tissue

13.  Bench to bedside. Ocular Surface Reconstruction. EX vivo transfer of limbal corneal stem cells

14.  Vitiligo- Tissue specific stem cells – for the treatment of the vitiligo.

15.  STEM CELL AND TISSUE ENGINEERING

CORNEAL DEFECT

LONG BONE DEFECT

16.  MSC are used for IBD where it has immunomodualtory capacity and the same MSC are used in Regenerative capacity. So is it the environment which determines the effect by which MSC will behave.

TCS-PGI SYMPOSIUM

TCS-PGI SYMPOSIUM

Reporting from the symposium. Important excerpts from the symposium

DATA IN SUPPORT OF THE CLINICAL USE OF ADIPOSE DERIVED MSC: GROWTH, STORAGE, FUNCTION AND SAFETY

WILLIAM A FAUBION MD

ALLAN B DIETZ Ph.D.

1.     GLP certified Phase 1 trial on the Adipose MSC on the undertaken currently.

2.     There are variety of products for which these Adipose MSC can be used like ALS, MSA, ARAS, Anal fistula, Crohn disease.

3.     Cells therapy are drugs. So it should be as much stable, reproducible and safe.

4.     They have patented a technology known as 5%PLTmax for developing stem cells which can be used with the properties which was mentioned in point 3.

5.     MSC can differentiate into Bone, Cartilage.

6.     The stem cells maintain their viability even when passed through various needles, and the population doubling is independent and not affected by frozen. This was proved.

7.     Safety issue? Tumour, how will it migrate, is it efficacious in the disease specified

8.     For testing the malignant transformation SCID mice is used, as the immunity should not interfere with the malignant transformation.

9.     On very high concentration of MSC, then also tumour did not form but increase collagen was formed

10.  The same high concentration MSC was injected intrathecal, intrarenal. These high concentration was purposefully injected to see for the potential of malignant transformation.

11.  For safety you have to test biometrics (measure the weight), all major organ pathology, study the behaviour and you have administered the MSC as mentioned in the point 9 and 10.

12.  Other important points to note in this preclinical study is that more than 70 animals used, 3 species, different route of injection

13.  EXCITING POINT: In ovarian tumour the stem cell is used as a Trojan war horse which carries the oncolytic virus to the ovarian cancer

14.  CONCLUSION: Don’t put the product in the patient untill all the technology is clearly understood. When a survey was undertaken, patient was preferring autologous over allogenate.

STEM CELLS IN POST SURGICAL GASTROINTESTINAL LEAK

NAVTEJ S BUTTAR MD

1.     Over 10 lakh gastrointestinal surgeries are done per year. So gastrointestinal leak is a common programme and there needs to be new good treatment for the same.

2.     Over Macro and Micro level changes are responsible for the gastrointestinal fistula.

3.     The micro level changes which are responsible is inflammation and Macro level changes are Age, obesity.

4.     Currently drain are used. Scaffold for filling the space is an important factor.

5.     This stem cells will not be used for fresh 2-3 day fistula, over these we use OTSC placement. These stem cells are mainly used for old fistula very difficult to treat.

6.     IDEA CAME FROM: Graham’s idea of using fat for the closure of the ulcer is used hear for the closure of the big fistula in the gut.

7.     With this idea of using adipose tissue for closing, the same logic was used for giving Matrix loaded SMC for closing the large fistula which are resistant to other treatment.

8.     STEMMIX TRIAL IN POST SURGICAL FISTULA is undertaken currently in the world.

AUTOLOGOUS MSC THERAPY OF PERIANAL FISTULIZING CROHN DISEASE

WILLIAM A FAUBION MD

1.     Form a treatment and research team around a patient problem. The inputs which these two teams will give a lot of translational potential.

2.     PROBLEM ATATEMENT: 1 perianal fistula occurred in 33 % of Crohns disease

60% of the patient does not respond to medical therapy. Available treatment is ineffective. Morbidity is significantly

3.     CURRENT THERAPY: Treatment of patient with Fibrin glue was one of the novel approaches but it is ineffective.

4.     Stem cells used for perianal fistula around the world.

5.     So this trial consists of

Seton placement, control of sepsis

After 6 weeks the Seton are removed the Mesenchymal loaded fistula plug is replaced in the place and fixed to fill it.

6.     Healing per drainage cessation was used for assessing the effectiveness of the treatment and Likert scale was used for evaluating it.

7.     Out of 9 patients who were evaluated untill now 8 patients have resolved and the problem recurred. But in one patient there is recurrence.

8.     EXCITING POINTS: In Bioengineering there are a list of compounds which can be used in humans what are those. These are important to use in research.

9.     Mesenchymal stem cells have immunomodualtory properties.

Breastfeeding may expose infants to toxic chemicals

Breastfeeding may expose infants to toxic chemicals

                   A recent research report conducted by Harvard has shown that a particular type of Chemical which is used to make pipes and other material resistant to the water is transferred to the young babies through breast milk. The study appeared online on August 20, 2015 in Environmental Science & Technology. The chemical name is PFAS. So on thinking what the effect of this is chemical on the Human body? It is well documented that PFAS is associated with reproductive toxicity, endocrine disruption and immune system dysfunction.

                   On seeing the type of research being conducted by which this is proved, it is by assessing the cause- effect relation. That is as the duration by which the mother breast fed increases, the level of the PFAS in the infant increases. As soon as the mother stopped breast fed, the level decreased. In partially breastfed patients, the level of the PFAS increased proportionately and not to the extent of fully breast fed infants.

                  But the authors are not  saying to stop breast feeding. The thing to note is that there is no legislation regulating the level of these chemicals in the water.

In rat model , the pathology of head injury can be divided into 2 types.

Caspofungin dosage

Day 1 loading dose: 70 mg IV infused over 1 hr (as a single dose)

Maintenance: 50 mg IV OD infused over 1 hr

Continue antifungal therapy for at least 14 days after last positive culture

It is hepatic eliminated . So no dose modification essential in impaired renal clearance

It has shown to be in equal efficacious to Amphotericin B but not superior to Amphotericin B

Least prices found in market:

Casfung from Glenmark (Critica) [Caspofungin]

Strength             Volume Presentation      Price*  

Casfung 50mg   1            Casfung INJ        8920.00  

Casfung 70mg   1            Casfung INJ        8920.00  

Casporan from Ranbaxy [Caspofungin]

Strength             Volume Presentation      Price*  

Casporan 50mg 1            Casporan INJ     7980.00  

Casporan 70mg 1            Casporan INJ     7980.00