The Science of Mesenchymal Stem Cells and Regenerative Medicine – Arnold Caplan PhD (VIDEO Part 1)

Professor Arnold Caplan of Case Western Reserve University is widely regarded as “The Father of the Mesenchymal Stem Cell”. This lecture is a “must see” for anyone interested in stem cell therapy. In Part 1, Prof. Caplan proposes a new regulatory pathway for approval of cell-based therapies and regenerative medicine called “Progressive Approval” to replace the current US FDA system that is now in place.

Prof. Caplan was speaking in Panama City, Panama at “La Medicina Del Futuro En El Presente”, an event organized by the honarable Ruben Berrocal MD, Minister of Science, Technology and Innovation SENACYT (National Secretariat of Science, Technology and Innovation) and Prof. K. S. Jagannatha Rao, Ph.D., FNASc, FABAP, FASB, FLS (Reino Unido) Director INDICASAT-AIP (Instituto de Investigaciones Cientificas y Servicios de Alta Tecnologia — Institute for Scientific Research and High Technology Services).

Arnold Caplan PhD of Case Western Reserve University and Riccardo Calafiore of Perugia University in Italy tour Medistem stem cell lab in Panama

Arnold Caplan PhD, Neil Riordan PhD and Riccardo Calafiore MD at Medistem Labs Panama

Arnold Caplan PhD, Neil Riordan PhD and Riccardo Calafiore MD at Medistem Labs Panama

Professor Arnold Caplan (left) and Professor Riccardo Calafiore (right) pose with Medistem Labs Panama Founder, Neil Riordan, PhD. Dr. Riordan is also the Founder of Stem Cell Institute in Panama City, Panama.

Prof. Caplan and Prof. Calafiore were in Panama City with Amit Patel MD to speak at “La Medicina Del Futuro En El Presente”, an event organized by the honarable Ruben Berrocal MD, Minister of Science, Technology and Innovation SENACYT (National Secretariat of Science, Technology and Innovation) and Prof. K. S. Jagannatha Rao, Ph.D., FNASc, FABAP, FASB, FLS (Reino Unido) Director INDICASAT-AIP (Instituto de Investigaciones Cientificas y Servicios de Alta Tecnologia – Institute for Scientific Research and High Technology Services).

Prof. Caplan is a Professor of Biology and General Medical Sciences (oncology) at Case Western Reserve University and the Director of the Skeletal Research Center at Case Western Reserve. Prof. Caplan is widely regarded as “The father of the mesenchymal stem cell”.

Prof. Calafiore is the Head of the Division of Endocrinology and Metabolism at the Medical School at the University of Perugia, Italy and Director of the Interdisciplinary Laboratory for Endocrine and Organ Transplant at the University of Perugia School of Medicine. He is also a director at ALTuCELL.

Amit Patel, MD, MS, is an associate professor in the Division of Cardiothoracic Surgery at the University of Utah School of Medicine and Director of Clinical Regenerative Medicine and Tissue Engineering at the University of Utah

Neil Riordan PhD is Founder of Stem Cell Institute in Panama City, Panama and the President of Medistem Panama. He is also CEO of Aidan Products.

The dual effect of MSCs on tumour growth and tumour angiogenesis

Michelle Kéramidas, Florence de Fraipont, Anastassia Karageorgis, Anaïck Moisan, Virginie Persoons, Marie-Jeanne Richard, Jean-Luc Coll and Claire Rome

Abstract (provisional)
Introduction

Understanding the multiple biological functions played by human mesenchymal stem cells (hMSCs) as well as their development as therapeutics in regenerative medicine or in cancer treatment are major fields of research. Indeed, it has been established that hMSCs play a central role in the pathogenesis and progression of tumours, but their impact on tumour growth remains controversial.

Our results suggest that hMSCs injection decreased solid tumour growth in mice and modified tumour vasculature, which confirms hMSCs could be interesting to use for the treatment of pre-established tumours.

Methods

In this study, we investigated the influence of hMSCs on the growth of pre-established tumours. We engrafted nude mice with luciferase-positive mouse adenocarcinoma cells (TSA-Luc+) to obtain subcutaneous or lung tumours. When tumour presence was confirmed by non-invasive bioluminescence imaging, hMSCs were injected into the periphery of the SC tumours or delivered by systemic intravenous injection in mice bearing either SC tumours or lung metastasis.

Results

Regardless of the tumour model and mode of hMSC injection, hMSC administration was always associated with decreased tumour growth due to an inhibition of tumour cell proliferation, likely resulting from deep modifications of the tumour angiogenesis. Indeed, we established that although hMSCs can induce the formation of new blood vessels in a non-tumoural cellulose sponge model in mice, they do not modify the overall amount of haemoglobin delivered into the SC tumours or lung metastasis. We observed that these tumour vessels were reduced in number but were longer.

Conclusions

Our results suggest that hMSCs injection decreased solid tumour growth in mice and modified tumour vasculature, which confirms hMSCs could be interesting to use for the treatment of pre-established tumours.

Original Link: http://stemcellres.com/content/4/2/41/abstract

Autologous bone marrow-derived cell therapy combined with physical therapy induces functional improvement in chronic spinal cord injury patients

Cell Transplant. 2013 Feb 26. [Epub ahead of print]

El-Kheir WA, Gabr H, Awad MR, Ghannam O, Barakat Y, Farghali HA, Maadawi ZM, Ewes I, Sabaawy HE.

Abstract

Spinal cord injuries (SCI) cause sensory loss and motor paralysis and are treated with physical therapy, but most patients fail to recover due to limited neural regeneration. Here we describe a strategy in which treatment with autologous adherent bone marrow cells is combined with physical therapy to improve motor and sensory functions in early-stage chronic SCI patients

In a phase I/II controlled single-blind clinical trial (clinicaltrials.gov identifier: NCT00816803), 70 chronic cervical and thoracic SCI patients with injury durations of at least 6 months were treated with either intrathecal injection(s) of autologous adherent bone marrow cells combined with physical therapy, or with physical therapy alone. Patients were evaluated with clinical examinations, electrophysiological somatosensory evoked potential, MRI imaging, and functional independence measurements.

Chronic cervical and thoracic SCI patients treated with autologous adherent bone marrow cells combined with physical therapy showed functional improvements over patients in the control group treated with physical therapy alone, and there were no cell therapy-related side effects. At 18 months posttreatment, 23 of the 50 cell therapy-treated cases (46 percent) showed sustained improvement using the American Spinal Injury Association (ASIA) Impairment Scale (AIS). Compared to those patients with cervical injuries, a higher rate of functional improvement was achieved in thoracic SCI patients with shorter durations of injury and smaller cord lesions.

Therefore, when combined with physical therapy, autologous adherent bone marrow cell therapy appears to be a safe and promising therapy for patients with chronic spinal cord injuries. Randomized controlled multicenter trials are warranted.

Endometrial regenerative cells for treatment of heart failure: a new stem cell enters the clinic

Leo Bockeria, Vladimir Bogin, Olga Bockeria, Tatyana Le, Bagrat Alekyan, Erik J Woods, Amalia A Brown, Thomas E Ichim and Amit N Patel

Journal of Translational Medicine 2013, 11:56 doi:10.1186/1479-5876-11-56
Published: 5 March 2013

Heart failure is one of the key causes of morbidity and mortality world-wide. The recent findings that regeneration is possible in the heart have made stem cell therapeutics the Holy Grail of modern cardiovascular medicine. The success of cardiac regenerative therapies hinges on the combination of an effective allogeneic “off the shelf” cell product with a practical delivery system. In 2007 Medistem discovered the Endometrial Regenerative Cell (ERC), a new mesenchymal-like stem cell. Medistem and subsequently independent groups have demonstrated that ERC are superior to bone marrow mesenchymal stem cells (MSC), the most widely used stem cell source in development. ERC possess robust expansion capability (one donor can generate 20,000 patients doses), key growth factor production and high levels of angiogenic activity. ERC have been published in the peer reviewed literature to be significantly more effect at treating animal models of heart failure (Hida et al. Stem Cells 2008).Current methods of delivering stem cells into the heart suffer several limitations in addition to poor delivery efficiency. Surgical methods are highly invasive, and the classical catheter based techniques are limited by need for sophisticated cardiac mapping systems and risk of myocardial perforation. Medistem together with Dr. Amit Patel Director of Clinical Regenerative Medicine at University of Utah have developed a novel minimally invasive delivery method that has been demonstrated safe and effective for delivery of stem cells (Tuma et al. J Transl Med 2012). Medistem is evaluating the combination of ERC, together with our retrograde delivery procedure in a 60 heart failure patient, double blind, placebo controlled phase II trial. To date 17 patients have been dosed and preliminary analysis by the Data Safety Monitoring Board has allowed for trial continuation.The combined use of a novel “off the shelf” cell together with a minimally invasive 30 minute delivery method provides a potentially paradigm-shifting approach to cardiac regenerative therapy.

http://www.translational-medicine.com/content/11/1/56/abstract

Allogeneic and autogolous stem cell therapy combined with physical rehabilitation: A case report on a chronically injured man with quadriplegia

Allogeneic and autogolous stem cell therapy combined with physical rehabilitation - A case report on a chronically injured man with quadriplegia

Daniel Leonard in Panama

This is a research paper written by Rebecca Johnston, Daniel Leonard’s sister. She recently graduated from a Physical Therapy degree program, and wrote her Capstone paper about Daniel’s stem cell therapy treatment in Panama.

Daniel is presented anonymously in the paper, but Rebecca and Daniel have given their permission for this paper to be shared. Daniel’s ASIA scores (pre and post treatment) are in the appendix of this paper.

 

Allogeneic and autogolous stem cell therapy combined with physical rehabilitation: A case report on a chronically injured man with quadriplegia

Abstract:

Background and Purpose: Stem cell therapy for SCI is a potentially promising treatment with increasing interest. This case report describes the use of a particular stem cell therapy protocol for a patient with chronic spinal cord injury, and describes his subsequent therapy and outcomes.

Case Description: The patient is a 29-year-old male who is chronically injured from a cervical spinal injury, resulting in quadriplegia. The patient was treated with a combined protocol of intrathecal (IT) and intravaneous (IV) allogeneic MSC and CD34+ cells and IT autologous BMMC at 6 ½ years post-injury. The results track the patient’s physical therapy progress until 6 months following stem cell treatment.

Outcomes: Recovery of strength in upper extremity and lower extremity muscle groups was noted, along with a functional increase in grip strength, ability to ambulate with assistance, and a significant decrease in daily medications.
Discussion: This case supports further investigation into treatment of chronically injured SCI patients with stem cell therapy followed by physical therapy.

Manuscript word count: 4321

A few highlights:

“After the patient underwent the stem cell treatment and returned to outpatient physical therapy in his hometown clinic in the United States, his MMT scores were tested over the period of 5 months post-stem cell treatment…. The patient did not decrease in strength in any of the muscles tested, and experienced improvements in 6/13 upper extremity muscle groups, and 8/9 lower extremity muscle groups.”

“The patient also had an increase in grip strength. His grip strength was measured by his occupational therapist to be 5 lbs on the right and 25 lbs on the left at one month before his stem cell treatment. Six months later, his grip strength was measured to be 22 lbs on the right and 36 lbs on the left. The patient reported that this increase in grip strength led to functional improvements, such as being able to self-catheterize, which he was completely unable to do since his injury.”

“The patient was also able to ambulate for the first time in 5 years at approximately 4 months after finishing his treatment. He was able to ambulate in partial weight bearing with the harness and max assist of two for 40 yards at .5 MPH.”


The original post on Daniel Leonard’s blog can be found here.

Mesenchymal Stem Cells in Regenerative Medicine:Mechanisms of action, sources, and delivery options

Neil Riordan, PhD, Founder of the Stem Cell Institute in Panama City, Panama will be speaking today, Wednesday, Feb 6 at the STEMSO International Stem Cell Society 2013 Conference in Fort Lauderdale, FL.

The topic of Dr. Riordan’s discussion will be “Mesenchymal Stem Cells in Regenerative Medicine:Mechanisms of action, sources, and delivery options”

The theme for this year’s event is “Autologous Stem Cells: Who gets to decide…”

Multiple Sclerosis Radio – “Stem cells are your body’s natural healing mechanism” – Neil Riordan PhD

For anyone who missed Dr. Riordan’s talk on MS Radio yesterday, below is a link to the replay. Did you know that by age 30, 96% of the mesenchymal stem cells are gone from a person’s bone marrow? Why is MS a disease of the immune system? How can an automated machine analyze a sample of lecithin and buffer that contains no cells and show that it contains 10 million cells per ml? Tune in for these and more.

REPLAY: “Stem cells are your body’s natural healing mechanism” – Neil Riordan PhD

TODAY ON MULTIPLE SCLEROSIS RADIO!
Dr. Neil Riordan, Founder of Stem Cell Institute
Tuesday Feb 5, 2013 at 2 pm EST.

LISTEN ONLINE: Multiple Sclerosis Radio

or call in Join Us LIVE On Air
(347) 327-9317
or Toll-Free
(877) 497-9936

http://www.blogtalkradio.com/msradio/2013/02/05/stem-cells-your-bodys-natural-healing-mechanism-stem-kine-1

Patients beware: “Point of care” fat stem cell separation and counting kits inaccurate and not US FDA approved for humans.

An informative paper by Mary Pat Moyer, PhD detailing why “same-day” fat stem cell kits that are becoming more common in doctors’ offices across the US can miscount “stem cells” by large factors leading to over estimation of stem cell counts by as much as 20 times or more.

It also states, “no complete harvest and cell isolation systems have been approved by the FDA for autologous SVF harvest for immediate use [in humans].” These are just a couple of the arguments presented that demonstrate why it’s important to process adipose tissue properly in a professional lab setting.

Morrison DG, Hunt DA, Garza I, Johnson RA, Moyer MP*. Counting and Processing Methods Impact Accuracy of Adipose Stem Cell Doses. BioProcess J, 2012; 11(4): 4-17.

Medistem Advances Type 1 Diabetes Stem Cell Technology Licensed From Yale

SAN DIEGO, CA — (Marketwire) — 09/12/12 — Medistem Inc. (PINKSHEETS: MEDS) announced today completion of the first phase of a joint project with the Shumakov Research Center of Transplantology and Artificial Organs of the Russian Federation and its Russian and CIS licensee ERCell. The collaboration is based on using Endometrial Regenerative Cell (ERC) technology licensed from Yale University to treat type 1 diabetes.

Dr. Viktor Sevastianov, Head and Professor of the Institute of Biomedical Research and Technology, within the Shumakov Center, demonstrated safety and feasibility of ERC injection in experimental animal models of diabetes. Additionally, the studies demonstrated that the cell delivery technology developed by Dr. Sevastianov’s laboratory can be used to enhance growth of ERC. These experiments are part of the process for registration of “new pharmacological substances,” which is the first step towards drug approval in Russia.
“Type 1 diabetes is a significant problem in the Russian Federation. Our laboratory has been working developing various delivery formulations for cell therapy, such as SpheroGel, which is registered in Russia,” said Dr. Sevastianov. “Given that the ERC can be produced in large quantities, is a universal donor cell, and already is approved for clinical trials in both the USA and Russia, we are optimistic our collaboration will lead to a viable commercial product for the type 1 diabetes Russian population.”
Medistem discovered ERCs in 2007, and they appear to possess “universal donor” properties, allowing the cells derived from one donor can treat multiple unrelated recipients. According to Medistem’s current FDA cleared production scheme, one donor can generate 20,000 patient doses. Medistem licensed technology from Yale University for generating insulin producing cells from ERC. A publication describing the technology may be found at http://www.ncbi.nlm.nih.gov/pubmed/21878900.

“Our vision is to combine SpheroGel, which is a clinically-available cell delivery vehicle in Russia, together with Medistem’s ERC and technology from Yale University to generate a commercially-viable product for clinical trials in type 1 diabetes patients,” said Thomas Ichim, CEO of Medistem.

Medistem has outlicensed the Russian and CIS rights to ERC and related products to ERCell LLC, a St. Petersburg-based biotechnology company. Under the agreement, Medistem owns all data generated and will receive milestone and royalty payments.
“By working with leading investigators in Russia and the USA, we seek to be the leaders in a new era of medicine in Russia,” said Tereza Ustimova, CEO of ERCell.”

Cautionary Statement This press release does not constitute an offer to sell or a solicitation of an offer to buy any of our securities. This press release may contain certain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified. Future events and actual results could differ materially from those set forth in, contemplated by, or underlying the forward-looking information. Factors which may cause actual results to differ from our forward-looking statements are discussed in our Form 10-K for the year ended December 31, 2007 as filed with the Securities and Exchange Commission.

Contact: Thomas Ichim Chief Executive Officer Medistem Inc. 9255 Towne Centre Drive Suite 450 San Diego, CA 92122 858 349 3617 www.medisteminc.com twitter: @thomasichim
Source: Medistem Inc.