Cardiac Disease

 

 

Urinary Incontinence

 

Chronic Fistulas (Crohn’s)

 

  

Skin Regeneration

  

 

  

 

 

 


 

 

 

 

 

 

 

 

 

 


  Regenerative Medicine 
 

 

"We are on the cusp of a worldwide explosion of activity in this rapidly growing field

that will revolutionize health care treatment".                                     

                                                       U.S. Dept of Health and Human Services, 2005

                                                                                                                    

Clinical experience with the use of ASCs to repair and regenerate tissues and organs continues to expand rapidly and in this section we present summaries of the latest peer reviewed publications.

 

Click on the left pane to read the summary texts and on the 1st author’s name to see the full reference in the Cryo-Lip bibliography. We will update the content regularly but an easy way to stay updated about recent publications is to subscribe to our quarterly Cryo-Lip eNewsletter.

 

 


Cardiac Disease

 


Several in vivo studies in different animal models have shown that ASCs can

 
  • improve left ventricular function in acute myocardial infarction
 Cai 2008
 
  • ASC's improve cardiac function chronic ischemia
 Léobon 2008
 
  • revacularize ischemic limbs
 Kondo 2008


This evidence led to clinical trials, the first of which started in 2007. Interim results for two studies were announced recently and are summarized below.

 

Duckers, H   Ongoing study, 1st results 2010

ASCs in Acute Myocardial Infarction, 

ClinicalTrials.gov Identifier: NCT00442806


 Design 

Randomized, placebo controlled trial in 48 patients

 

                   Inclusion  Acute MI (within 24 hrs) with ST elevation
   Endpoints    primary     safety
 secondary   assessment of cardiac function via functional and imaging studies
    
 Method Injection of ASCs obtained from liposuction on same day vs placebo injection
    
 Results 6 months results, presented at Int Symposium on Stem Cell Therapy & Cardiovascular Innovation in Madrid, 2010
   

Mean infarct size                 ASC group reduced from 32% to 15% vs no change in placebo group at 25%

Left ventricular perfusion     3.5 times improved in ASC group vs 1.7 in placebo

Ejection fraction                  6% improvement with ASCs vs -2% in palcebo group

   
  Conclusion Dramatic improvements at 6 month follow-up promise a new way to treat acute MI.
Longer term follow-up ongoing.
    

 

Fernandez-Avilez, F Ongoing study, 1st results 2010ASCs in Chronic Myocardial Ischemia,
ClinicalTrials.gov Identifier: NCT00426868

 

 Design          Randomized, double blind, placebo controlled trial in 27 patients 
  Inclusion  No option coronary artery disease, life expectancy > 1 year 
  Endpoints    primary        safety
secondary    assessment of cardiac function via functional and imaging studies
 
     
 Method Injection of ASCs obtained from liposuction vs placebo injection 
     
 Results 6 months results, presented at Int Symposium on Stem Cell Therapy & Cardiovascular Innovation in Madrid, 2010  
   Liposuction and ASC injection were safe with no SAEs  
   

Max O2 consumption     MVO2 increase in ASC group vs deterioration in placebo (p < 0,05)

Aerobic capacity           improved by 0.2 points in ASC group vs deterioration in placebo of 0.8 (p < 0,05)

Severity heart disease   improvement of  66% vs 33% in favor of SC group

 
     
 Conclusion Encouraging results in difficult patient group, consistent with preclinical evidence.
longer term follow-up ongoing.
 
     


Skin Regeneration

 


 

ASCs have been shown to have positive effects in skin repair and regeneration, and the first summary below highlights the mechanisms of action. In vivo evidence and first reports of benefical effects in skin ageing and anti-wrinkle effects follow.

 

Kim, WS    Expert Opin Biol Ther2009The wound healing and antioxidant effects of ASCs

 

  Synopsis 

Recent research developments show clear wound healing and antioxidant effects of ASCs.

ASCs do not differentiate into skin skin cells, but work mainly in a paracrine way by secreting cytokines and growth factors.

Skin repair effetcs are mainly mediated by the activation of dermal fibroblasts and keratinocytes.

    
 Conclusion ASCs show great promise for use in skin repair and regeneration
    
   

 

Nambu, M    Ann Plast Surg    2009   ASCs accelerate wound healing in diabetic healing-impaired mice

 

     Design      

Controlled experiment, n = 12, two full thickness round skin defects.

Histologic sections evaluated after 1 and 2 weeks.

    
 Results  ASC group significantly improved granulation tissue, capillary formation and epithelialization.
    
 Conclusion In vivo evidence show ASCs significantly accelerate wound healing
    
   

 

 Park, BS      Derm Surg          2008 ASCs and their secretory factors  a promising therapy for skin aging

 

       Synopsis      

In vivo part of study showed that ASCs prodcue many useful growth factors, including collagen production.

 

In a case study that followed one patient showed reversal of skin aging.

    
 Conclusion ASCs show promise in the treatment of skin aging
    
   

 

 

 

Urinary Incontinence


 

 Mitterberger, M J Urol 2008 Autologous MSC therapy for post-prostatectomy urinary incontinence                  

 

        Design 63 males with SUI after radical prostatectomy, treatment trial, 1 year follow-up
    
        Method 

Transurethral ultrasound guided injections of autologous MSCs (fibroblasts and myoblasts)

Measured urodynamics, incontinence, QoL, morphology and function of urethra and rhabdosphincter

    
 Results After 12 months 41 patients were continent, 17 improved and 5 no change
    
 Conclusion MSC therapy is minimally invasive, safe and effective for post-prostatectomy incontinence
    
   

 

Yamamoto,T Int J Urol 2009 Periurethral injection of ASCs for urinary incontinence after radical prostatectomy

 

        Design 

Two patients with moderate stress incontinence after radical prostatectomy

12 week follow-up

                                                                                                                                                        
 Method ASCs obtained via abdominal liposuction (250 ml)

Injected transurethrally with adipose tissue into rhabdosphincter and submucosa

    
 Results 

Urinary incontinence progressively improved as measured by
 - 24-h pad test, frequency and volume

 - maximum urethral closing pressure and functional profile length
 - Quality of Life questionnaire

 - no adverse events

    
  Conclusion Local injection of autologous ASCs is feasible and safe treatment for SUI 
    
   

 

 

Chronic Fistulas (Crohn's)

 


 

Several preclinical and in vivo studies have shown why ASCs could be effective in Crohn's disease and and provided the basis for the cliniacl trials that folloowed. Below is a summary of one such in vivo study, followed by clincal reports.

 

Gonzalez-Rey, E  GUT2009  ASCs alleviate experimental colitis by inhibiting inflammatory responses

 

          Method            Mice with induced colitis were treated with hASCs after onset of disease. Clinical scores as well as inflammatory response  and different inflammatory mediators were evaluated.
    
  Results 

hASCs improved the clinical severity of colitis, weight loss, diarrhea, and survival (P < .001).

They also decreased a wide panel of inflammatory cytokines and chemokines (P < .001), directly acting on activated macrophages. hASCs also impaired Th1 cell expansion (P < .001).

 

    
  Conclusion  hASCs are attractive candidates for a cell-based therapy for Crohn's disease
    
   

 

 

Garcia-Olmo, D   Int.J.Colorectal Dis.   2003   Autologous SCs for Rx of rectovaginal fistula in perianal Crohn's disease

 

      Method

 

Case report of young woman with recurrent rectovaginal fistula.

ASCs obtained as lipoaspirate were used as a surgical autotransplant.
    
 Results No vaginal flatus or fecal incontinence after 3 months.
    
 Conclusion  ASCs seem to be effective, with no ethical and safety problems using autologous SCs
    
   

 

Garcia-Olmo, DExpert. Opin. Biol. Ther.2008Expanded ASCs in complex perianal fistula: a phase II clinical trial

       Design         

Phase IIb multicenter, randomized controlled trial.

49 patients with complex perianal fistulas (of which 14 with Crohn's disease).

    
  Method 

Intralesional treatment with fibrin glue or fibrin glue plus 20 million ASCs (derived from lipoaspirate).

Fistula healing and quality of life (SF-12 questionnaire) were evaluated at eight weeks and one year.

    
  Results 

Fistula healing in (71%) in ASC group vs 16% in fibrin glue alone group (relative risk 4.43,  P < 0.001). 

No difference in Crohn's vs non-Crohn's subgroups. 
QoL scores were also higher in the ASC group with a recurrence rate of 17.6% after one year.

Both treatments were well tolerated.

   

 

  Conclusion ASCs with fibrin glue is an effective and safe treatment for complex perianal fistula
    
   

 




"I have no doubt that adipose-derived stem cells will play an important role

in the future of both regenerative medicine and cosmetic surgery"

 
Dr Jorge Planas, Barcelona, Spain