Dear Fadi,
We recently have proposed a 'Transcribrial Route' and a device for delivery through the upper part of nasal cavity, for Neurodegenerative diseases. The weblink below.
Kindly feel free to inquire more if needed.
Med Hypotheses. 2014 Oct;83(4):510-2. doi: 10.1016/j.mehy.2014.08.003. Epub 2014 Aug 11
We have delivered MSC via percutaneous injection into fracture sites to promote healing.
Hi Dr. West, have you published the outcome of this technique and application in humans? can you add it here. Thanks
We are currently in the process of setting up a trial for intramuscular and subcutaneous injections for digital ulcers.
Other routes that are commonly used are:
- IM (as mentioned)
- Intraarterial (for instance in peripheral arterial disease)
- Intracoronary (artery)
- Intramyocardial
- As mentioned above indeed intranasal (afaik animal only up till now).
- Intrathecal (spinal canal)
And lastly there are many studies investigating tissue engineerd constructs using MSCs for e.g. bone, cartilage, bladder etc.
To my knowlegde are IM injections the best in terms of cell retention as IV injection leads to collection (and embolism) of MSCs in the lungs. It doesn't seem to affect efficacy though. For animal studies you might want to look at meta-analyses of cell therapy in the heart (e.g. van der Spoel et al., cardiovasc. res) or kidney (Papazova et al. Dis mod. mech, 2015), they do meta-regression on delivery route to identify optimal delivery route.
Hi
we injected into spinal cord injury site by Hamilton syringe after filtering to promote healing.
Hi
There are several routes which each of them has their own advantages and disadvantages.The important matter is having the ability for clinical translayion and patient compliance..So the iv is less invasive than others such as ip or intracranial or intra arterial or......Besides that the paracrine effect of stemcells can have the advantages as homing effect.
Hi Fadi
I agree to the comments by Hendrik Gremmels.
You should distinguish between different approaches:
- topical/regional
- systemic
- scaffold/bioengineered constructs
For topical application cell-spray, gel or subcutaneous injection with a carrier hydrogel may be an option. Regional application is through intraarterial injection with cells getting captured in an organ capillary system or tissue. For systemic application iv, intraarterial and intrathecal as well as inhalation are options. Intraosseous injection is somewhere in between systemic an topical treatment, which is the same for intramuscular application. My personal experience with i.m. injections is not very promising als cells migrate and tend to leave the injection site (at least in scelettal muscle - this may be different in heart). The fate of MSCs after peripheral topical application is widely unknown. To my knowledge they did not show accumulation after topical treatment. Also bioengineered construct (vascular grafts) are available. For the systemic applications the paracrine function of MSCs is said to be the main functional mechanism as many cells will be entrapped in the lung capillaries, where they accumulate and express a variety of growth factors and cytokines.
I agree with the distinguished answers previously given. However, no matter what route you choose one of the key critical issues for a successful response relates to the number of stem cells given, e.g., the effective dose (ED). We found that the ED for stem cells (mesodermal or others) needs to be greater than or equal to 1 million cells per cubic centimeter (CC) of tissue to be treated.
The point raised by Dr Young is very interesting. I agree that the ED is of major importance. In clinical studies a minimum of 1Mio cells/kg bodyweight is frequently used. ED studies in humans are currently still lacking to my knowledge. In our previous studies in mice we saw a dose dependent effect (Schweizer et al. Cytotherapy. 2014 Jun 24. pii: S1465-3249(14)00606-9), which was not equalled with conditioned medium. Nevertheless I do believe that the ED is also dependent on the indication for treatment. For regenerative indications or topical treatment the dose should be different in comparison to systemic immunomodulation.
Dear Jan,
We have two papers published from a safety and efficacy human clinical trial we ran with Parkinson disease. We utilized the formula I gave previously, 1M cells per cc tissue treated, giving a minimum of 5 billion totipotent stem cells intranasally and a minimum of 5 billion pluripotent stem cells by IV. One month following a single treatment with these autologous adult stem cells 100% of the participants demonstrated positive results. We also measured outcomes at 7 months and 14 months post transplant. In both instances 75% of the participants continued to show positive results. We stopped the proposed 24-month study at the 14-month time point so that some of the participants could receive additional transplants, which they did. Those particular individuals went from demonstrating moderate to severe Parkinson symptoms to smiling and taking long (normal) walks with their spouses. Our previous work in animal models (reviewed in the Bench Top to Beside paper) demonstrated that the cells actually incorporated into the tissue and regenerated the missing and/or damaged cells. So the affect of endogenous adult-derived totipotent stem cells and pluripotent stem cells on the tissue is not just immunomodulatory, but also regenerative.
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