How are the cells processed and are they safe?
The umbilical cord is processed in the hospital according to the rules and regulation of the American Association of Tissue Banks (AATB). Approximately 4 weeks prior to a scheduled caesarean section, the mothers OB/GYN asks her if she would like to keep and store her unborn child’s umbilical cord for future use. If the mother declines then she is asked if she would like to donate the umbilical cord. If she agrees, she undergoes a review of her medical history, social history, and a blood test. If she is deemed an acceptable donor according to prevailing rules of the AATB, then at the time of her caesarean section an experienced technician will clamp the umbilical cord, take it to a clean room, and remove the contents of the umbilical cord and place it into a blood bag. The bag of umbilical cord blood is then delivered to the lab for processing. Once at the lab, a sample of the umbilical cord blood is sent to a 3rd party independent FDA registered lab for testing according to United States Pharmacopeia rule 71 (U.S.P. 71), which is a test for known communicable diseases. While that test is taking place the stem cells are then processed and removed from the red blood cell products. A sample of the finished stem cell product is then sent to a different 3rd party independent FDA registered lab for sterility testing. Only after both lab reports come back as “clean” and have passed the regulatory requirements, are the processed umbilical cord stem cells available for distribution.
Do you ever use an aborted fetus?
No, we only use the umbilical cord from a live healthy birth baby.
Is HLA matching necessary?
No, HLA matching is not necessary for the Liveyon product because HLA-DR, the component responsible for a non-HLA matched negative reaction, is below measurable amounts. Even in the 1990’s when HLA-DR extraction techniques were far less efficient than they are today, negative HLA-DR reactions were not commonly seen.
How are the Cells Delivered?
The cells will be delivered via FedEx on dry Ice (-80 C) in a Styrofoam container and an outer cardboard box. The package will arrive by approximately 10:30 am on the requested delivery date
How Long Will the Cells Survive on the Dry Ice?
The container with the dry ice should maintain -80 C for at least 48 hours but is dependent upon the environment in which it is stored. If for some reason the procedure cannot be performed on the originally scheduled day, you can purchase dry ice at a local supermarket and continue to refill the container. The cells will maintain viability as long as they are covered in dry ice and maintained at -80 C.
Can I Split the Contents of the Vial on the SAME Patient?
Yes, you may split the contents of a vial on the same patient. For example, if you order the 30 million concentration vial, you may split the vial and inject the equally divided contents into 2 or 3 joints for the desired minimum of 7 to 10 million cells per medium to large size joint.
Can I Split the Contents of the Vial on DIFFERENT Patients?
No, you may NOT split the contents of the vial and use on 2 different patients. For regulatory and tracking purposes, the vials are SINGLE USE and can only be used on a SINGLE PATIENT.
What is the Desired Lead Time to Order Cells?
The Liveyon order department must receive your order by 1 PM Pacific Time the day BEFORE you need the cells. The Order will be processed and shipped overnight for a 10:30 AM delivery the day of the proposed procedure.
Can I Order Product Sooner Than the Day Before?
Yes. When filling out your purchase order form you may order as far in advance as you would like. Your order will be recorded and shipped the day before your requested delivery date.
Can I Store the Cells at my Office?
Yes, as long as you store them at -80 C. We have commercially available -80 C freezers that will allow you to buy in bulk and have the cells available for immediate use. The freezer option will also save you shipping costs associated with multiple monthly shipments.
Is DNA testing necessary?
No, DNA testing is not necessary because the stem cells and mononucleated cells do NOT penetrate the nucleus of the recipients’ cells and thus do not pass on DNA. The ability of a stem cell to pass along DNA matter is a property of a stem cell when it is in the embryonic stage and is no longer possible after the 10th week of gestation. Umbilical cord stem cells are harvested between weeks 36 and 40.
The International Society for Cellular Therapy (ISCT) says that the presence of CD90, CD105, and CD73 are necessary for the identification of stem cells, why do you only test for the presence of CD90?
The definition by the ISCT is for pure stem cells and not a heterogenous mix of stem cells and mononucleated cells that are used for umbilical cord stem cell therapies. It is also noted in literature that the presence of one or all the CD’s consistent with the presence of stem cells is an indicator of stem cells. The reason we chose to test for CD90 is because it is the most clinically relevant for our purposes. CD90 is implicated in axonal growth, T-cell activation, cell adhesion, cell migration, and cell extravasation while CD105 is implicated in hematopoietic stem cell (HSC) function and CD73 is implicated in tumor suppression.
Do Stem Cells duplicate themselves in the body?
No, stem cells do NOT duplicate themselves in the body. Stem cells DO have the ability to duplicate themselves in vitro, in culture in the lab, but they do NOT duplicate themselves in the body. This is a long-held myth that is now disproven.
Do Stem Cells cause cancer or cause cancer to grow?
No, the fact that stem cells do not duplicate themselves within the body is a major reason that stem cells do not proliferate nor cause cancer to grow. Multiple studies are being done around the world showing that stem cells can actually fight cancer and stop the growth of cancer cells. This research is ongoing and the exact effects of stem cells for the treatment of cancer is, as of yet, unknown.
Do allogeneic stem cells differentiate/change into new tissue in my body?
No, stem cells do NOT differentiate/change into new tissue in your body. Stem cells produce long-term effects by responding to signals from injured tissue. The stem cells work by inhibiting the inflammatory components that cause pain and damage to tissue and the mononucleated cells secrete growth factors, proteins, and cytokines that stimulate our own native tissue to repair and regenerate itself.
Are Umbilical Cord Stem cells from another person safe to put into my body?
Yes, allogeneic (taken from another person of the same species) cells are safe to put into your body. When the umbilical cord is processed, all the red blood cell components that could cause a negative reaction are removed. Also, the umbilical cord cells are naïve/immature and do NOT react the way a mature adult cell would act.
“Mesenchymal stem cells produce huge quantities of bio-molecules, some of which are immunosuppressive; MSC’s put up a curtain of molecules around themselves that allows donor (allogenic) MSC’s to be transplanted into a recipient, free from an immune response. (Immune privileged/Immune Masked)”
Arnold Caplan, PhD. Case Western Reserve University. Experimental and Molecular Medicine (2013) 45 Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine
Are Umbilical Cord Cells the same as Amniotic fluid?
No, umbilical cells are LIVE NUCLEATED CELLS that contain stem cells that will continue to produce anti-inflammatory and immunomodulatory components that optimize the local cellular environment. They also contain mononucleated cells that produce growth factors, proteins, and cytokines that stimulate our own tissue to regenerate itself. Because the cells are LIVE, they can continue to exert the cellular function for weeks and even months in the body.
Conversely, amniotic fluid/tissue must be processed in such a way that KILLS the live nucleated cells leaving a product that contains growth factors, proteins, and cytokines that will have an effect for several hours to a few days.
Are Live Nucleated Cells Important?
Yes, the presence of live nucleated cells means that the anti-inflammatory and immunomodulatory components from the MSC’s will continue to be produced for many weeks and months, optimizing the injured environment. At the same time, the growth factors, proteins, and cytokines produce by the mononucleated cells will stimulate our own endogenous tissue to repair and regenerate itself.
Are there other Stem Cell products that contain Live Nucleated Cells?
Yes, bone marrow aspirate and adipose derived stem cells also contain live nucleated cells.
Are all Live Nucleated Cells created equal?
No, live nucleated cells from umbilical cord blood are young, vibrant cells that have not been effected by age or disease whereas bone marrow aspirate and adipose derived stem cells are significantly older and potentially damaged by disease.
Does Age Matter?
Yes, age definitely matters. In Vitro research by the International Journal of Molecular Sciences has shown that while young, vibrant umbilical cord stem cells can duplicate themselves every 28 hours for up to 65 generations or more, 50+ year old bone marrow aspirate and adipose derived stem cells duplicate at a much slower rate of 3 to 5 days for an average of only 11 to 13 generations. Also of note is that older cells undergo senescence (aging) at a much faster rate than young, vibrant umbilical cord cells and older senescent cells produce less quantities and less effective growth factors, proteins, and cytokines.
Int. J. Mol. Sci. 2013, 14, 17986-18001; doi:10.3390/ijms140917986. International Journal of Molecular Sciences ISSN 1422-0067 www.mdpi.com/journal/ijms
How Do Umbilical Cord Stem Cells Actually Work?
When umbilical cord cells are placed into an environment of injured tissue, the stem cells go to work inhibiting the damaging inflammatory components and modulating the immune system. At the same time, the mononucleated cells produce growth factors that nourish damaged cells back to health and stimulate our own cells to regenerate themselves.
What Size of Needle Should I Use?
After thawing the cells in the palm of your hand for 3 to 4 minutes, it is easiest to draw the cells into a syringe using an 18-gauge needle.
For injection, you may use the needle of your choice. Ex. 20, 22, 23, 25 gauge etc.
Can I Use a Local Anesthetic?
Local anesthetics may be used to numb the needle pathway however you do NOT want to infuse large amounts of any local anesthetic into the joint or area being treated.
Likewise, you do NOT want to directly mix local anesthetic with the cells in the syringe.
Are Any Anesthetics Better To Use Than Others?
Yes, there is some research showing that ‘sodium channel blockers’ (lidocaine, carbocaine etc.) have a damaging effect on the nucleated cells whereas the ‘amide group’ of local anesthetics (Marcaine, bupivacaine, ropivacaine) do not have the same damaging effect.
Do I Need to Mix/Dilute the Umbilical Cord Cells Before Injection?
No, the cells may be injecting directly into the desired area without any dilution
Can I Mix/Dilute the Cells Prior to Injection?
Yes, you may mix/dilute the cells with PRP, which is isotonic and contains growth factors so it can increase the anti-inflammatory component.
You may mix/dilute the cells with normal saline (0.9%) if you wish but understand that a certain amount of hyperosmolality will take place and up to 10% to 15% of the cells could lyse. The lysed cells will still exert the function of the growth factors, by only for the half-life of that growth factor, similar to amniotic fluid. (Cell death from the use of saline and thawing is considered when the cells are initially concentrated so that you will have the labeled number of cells after both processes)
What is the Best Method for Thawing the Cells?
Multiple methods of thawing, at the clinical level, have been studied and the easiest most effective method is by placing the vial in the palm of your hand (or the patient’s hand) for 3 to 4 minutes. This should only be done once the patient is ready to be prepped for the procedure.
Is There a Special Protocol/Method for Injecting Stem Cells?
YES AND NO. You inject the cells into the desired area the same way as any other injection, the difference is in preparation.
DO NOT thaw the cells until the patient is present AND ready to be prepped for the injection. Remove the package containing the cells from beneath the dry ice. Remove the vial from the packaging and place in the palm of your hand (or the patient’s hand) until the cells are thawed. (Approximately 3 to 4 minutes). Using aseptic technique, draw the cells into a syringe using an 18-gauge needle. (Use a syringe size that will hold the cells, with or without a dilution product. The 18- gauge needle is for ease of drawing the cells into the syringe, a smaller needle will NOT damage the cells). Prep the patient and inject the cells into the desired area as soon as possible using the needle size of your choice. Ie. 20, 22, 23, 25 gauge etc.
Research has shown that cells begin to die within minutes of being thawed, so be expeditious in the injection process. (Cells will survive longer in PRP due to its isotonic nature vs. mixed with saline or by themselves)
Are There Specific Numbers of Cells Necessary to Treat Different Problems?
Yes, Worldwide research over almost 20 years has given us some effective parameters.
Large to medium joints: (Shoulder, hip, knee, ankle) 7 to 10 million cells/joint
Small joints: (Elbow, 1st MCP/MTP, etc.) 2.5 to 5 million cells/joint
(It should be noted that when injecting smaller joints, it is very important to NOT damage the cartilage upon entry into the joint. Many clinicians will place the cells peri-articular around the small joints to avoid cartilage damage to the joint. The cells will migrate into the joint)
Soft Tissue: (epicondyles, tendonitis/osis, partial tendon/ligament tears etc.)
5 million cells have shown to be very effective/site
(When injecting for a damaged ligament or tendon, it is most effective to inject around the site and not actually into the damaged tendon or ligament to avoid further needling damage)
Intra-disc: 15 million cells/disc
Clinical trials have shown 14 million cells to be very effective, so typically, when doing a single level disc injection, you will also inject the corresponding Facet Joints along with 1 level above and 1 level below. Example: Use 1⁄2 of the vial, 15 million cells, to inject into the desired disc. (you can add PRP for some volume and 1⁄2 to 1cc of hyaluronic acid for viscosity) Using the other 1⁄2 of the vial, add enough PRP or saline to inject 1cc of stem cell/PRP solution into each of the 6 corresponding facet joints. IF you are injecting 2 discs, then you will split the 30 million cell preparation evenly between each disc and if you desire to inject the corresponding facet joints along with 1 level above and below, (8 facets) you would add 7 cc’s of PRP or saline to a 1 cc vial of the 10 million cell concentration and inject 1cc into each facet. It should be noted that if the facet joint is collapsed, peri-articular injection is quite effective for the desired peripheral anti- inflammatory effect.