Cell Transplantation (Mesencephalic, Adrenal-Brain and Fetal Xenograft) - CAM 075HB

This document addresses adrenal-brain, fetal mesencephalic and fetal xenograft transplantation which have been proposed as treatments to modify the symptoms and disability of advanced Parkinson's disease.

Parkinson's disease is a progressive, incurable, disabling disease caused by slow continuous loss of nerve cells in a part of the brain called the substantia nigra that produces dopamine, a brain chemical critical for movement of the body. According to the National Institutes of Health (2011), approximately 1 to 2 percent of adults over the age of 60 are affected by Parkinson's disease.

Common symptoms of the disease include tremors or involuntary movement in the jaw and extremities, slowed movement, muscle stiffness, gradual loss of voluntary movement, gradual loss of automatic movement, postural instability and depression. The exact cause of Parkinson's disease is not known, but there is some evidence that there may be an inheritable component to the disease. 

At this time, there is no known cure for Parkinson's disease. Primary management of the disease is through pharmacologic therapies. No drug has been shown to effectively slow the progression of the disease. As Parkinson's disease progresses, pharmacotherapy becomes less and less effective in managing the symptoms of the disease. Surgical procedures such as pallidotomy and electrical deep brain stimulation may be considered for severe cases. However, none of these treatments correct the underlying problem of nerve cell degeneration.

Several techniques have been proposed for the treatment of the underlying cause of Parkinson's disease in which tissue or cells from other sources are transplanted onto the candidate's brain at the location where cell degeneration is occurring or in nearby areas. Theoretically, the transplanted cells take the place of the dysfunctional brain cells by producing dopamine, thus improving the signs and symptoms of Parkinson's disease.

The transplantation of tissue from the adrenal glands, specifically adrenal medullary tissue, to a portion of the brain called the corpus striatum, called adrenal-to-brain transplantation, is intended to improve the motor and postural dysfunctions of Parkinson's disease. Adrenal-to-brain transplantation can involve either an autograft from the candidate or an allograft from an aborted fetus. When done with the individual's own adrenal tissue, a complicated double surgery, one to remove the adrenal tissue, and one to transplant it into the brain, is required.

Another type of transplant for Parkinson's disease, fetal mesencephalic transplantation, involves a surgical procedure to implant tissue harvested from fetal brains, specifically mesencephalic tissue, into portions of the candidate's brain known as the caudate and putamen areas.

Finally, surgery to transplant brain tissue from fetal pigs (e.g., xenografts) into the brains of individuals with Parkinson's disease has also been attempted. The goal of this procedure, as with the other procedures described, is to implant dopamine-producing cells into the brain, alleviating the symptoms of the condition.

Adrenal-to-brain transplantation with autograft or fetal allograft is considered investigational and/or unproven and is therefore considered NOT MEDICALLY NECESSARY in all cases.

Fetal mesencephalic transplantation for the treatment of Parkinson's disease is considered investigational and/or unproven and is therefore considered NOT MEDICALLY NECESSARY .

Transplantation with fetal xenografts (e.g., from pigs or other animals) for the treatment of Parkinson's disease is considered investigational and/or unproven and is therefore considered NOT MEDICALLY NECESSARY.

Parkinson’s disease (PD) is a motor system disorder resulting from the loss of dopamine-producing cells in the midbrain that innervate the caudate and putamen. Symptoms include resting tremor, rigidity, and the impaired ability to start and continue bodily movements. Because pharmacologic treatment does not provide sufficient long-term therapeutic benefit, surgical interventions to transplant dopamine-producing tissues into the brain are under study.

At this time, the medical literature regarding adrenal-to-brain transplantation for the treatment of PD is limited to the description of uncontrolled, short-term studies with small sample sizes or case studies. Although some of these studies report finding clinical improvements, high morbidity and mortality rates are frequent. A few pathologic reports on adrenal-to-brain recipients demonstrated very few to no surviving transplanted cells 6 months to a year following surgery. Due to the lack of long-term outcomes or data from large controlled randomized trials, in conjunction with reports of high rates of complications and death in the existing literature, studies investigating adrenal-to-brain transplantation for the treatment of PD have diminished.

The evidence for the clinical impact of fetal mesencephalic transplantation is inadequate to support conclusions. Concerns related to small sample sizes and a limited number of controlled trials are joined with a wide array of methodological issues with the procedure itself.

The medical literature currently describes several different surgical approaches, such as open or stereotactic, and bilateral versus unilateral, in addition to variations in tissue preparation methods, the number of transplants, inclusion or exclusion of postoperative immunosuppressive therapy, and the type of screening used for tissue donors. While this procedure demonstrates low morbidity and mortality, significant improvements in short- and long-term physical symptoms, and graft viability and function is maintained, with such a wide range of methods available and low level of evidence to support each, there is inadequate support for any one method at this time.

Investigations into the use of porcine fetal mesencephalic transplantation are being conducted. While similar methodological issues exist as with human fetal tissue transplantation, fewer concerns related to the use of porcine fetal tissue may make this type of procedure more widely accepted. At this time, only a few small clinical trials have been described in the literature with some promising results. Further randomized controlled studies must be conducted before this type of therapy may be adequately evaluated for use and long-term efficacy in the clinical setting.

The International Parkinson and Movement Disorder Society ([MDS]; Fox, 2011) updated their evidence-based medicine review of treatments for motor symptoms of PD. The MDS concluded that surgical outcomes of human fetal cell transplantation as a treatment for PD was investigational and evidence on efficacy was insufficient. In 2013, the MDS updated their Position Paper on the use of stem cell therapies for PD, reconfirming their earlier conclusion that human fetal cell transplantation remains investigational.

The MDS published a position paper in 2021 on stem-cell based therapy for PD. The authors summarized the following position and recommendations:

Cell-based therapies should demonstrate efficacy and safety particularly lacking adverse immune reactions, tumor formation or dyskinesias. There have been great advances in the research of stem-cell therapy, especially for PD, and clinical trials are ongoing. However, for the time being there is still not enough evidence to support the widespread use of cell-based therapies for PD outside of carefully controlled clinical trials. We are hopeful for the future progress of such therapies based on extensive translational studies in proper animal models, and international clinical approaches with properly designed trials. (Brundin, 2021).

While transplantation of tissues from the adrenal gland (adrenal-to-brain), fetal mesencephalic allograft and fetal xenografts have been proposed as a replacement source of dopamine-generating neurons to treat individuals with PD, data are lacking regarding the long-term safety and effectiveness of these proposed therapies and further randomized controlled studies must be conducted before this type of therapy may be adequately evaluated for use in the clinical setting.

Autograft: The process of taking tissue from one part of the body and transplanting it into another part of the body with the goal of treating some specific disease or condition.

Fetal Allograft: The process of taking tissue or cells from an aborted fetus and transplanting it into the body of a recipient with the goal of treating some specific disease or condition.

Mesencephalic: Pertaining to the mid-section of the brain.

Xenograft: The process of taking tissues from another species, such as pigs, transplanting it into the body of a human with the goal of treating some specific disease or condition.


  1. Bhattacharya N, Chetri MK, Mukherjee KL, et al. Can human fetal cortical brain tissue transplant (up to 20 weeks) sustain its metabolic and oxygen requirements in a heterotopic site outside the brain? A study of 12 volunteers with Parkinson's disease. Clin Exp Obstet Gynecol. 2002; 29(4):259-266.
  2. Drucker-Colin R, Verdugo-Diaz L. Cell transplantation for Parkinson's disease: present status. Cell Mol Neurobiol. 2004; 24(3):301-316.
  3. Fillmore HL, Holloway KL, Gillies GT. Cell replacement efforts to repair neuronal injury: a potential paradigm for the treatment of Parkinson's disease. NeuroRehabilitation. 2005; 20(3):233-242.
  4. Fink JS, Schumacher JM, Ellias SL, et al. Porcine xenografts in Parkinson’s disease and Huntington’s disease patients: preliminary results. Cell Transplant. 2000; 9(2):272-278.
  5. Freed CT, Greene PE, Breeze RE, et al. Transplantation of embryonic dopamine neurons for severe Parkinson’s disease. N Engl J Med. 2001; 344(10):710-719.
  6. Jankovic J. An update on the treatment of Parkinson's disease. Mt Sinai J Med. 2006; 73(4):682-689.
  7. Kefalopoulou Z, Politis M, Piccini P, et al. Long-term clinical outcome of fetal cell transplantation for Parkinson disease: two case reports. JAMA Neurol. 2014; 71(1):83-87.
  8. Lindvall O, Kokaia Z. Stem cells for the treatment of neurological disorders. Nature. 2006; 441(7097):1094-1096.
  9. Ma Y, Feigen A, Dhawan V, et al. Dyskinesia after fetal cell transplantation for Parkinsonism: a PET study. Ann Neurol. 2002; 52(5):628-634.
  10. Olanow CW, Gracies JM, Goetz CG, et al. Clinical pattern and risk factors for dyskinesias following fetal nigral transplantation in Parkinson's disease: a double blind video-based analysis. Mov Disord. 2009; 24(3):336-343.
  11. Schumacher JM, Ellias SL, Palmer EP, et al. Transplantation of embryonic porcine mesencephalic tissue in patients with PD. Neurology. 2000; 54(5):1042-1050.
  12. Schwarz J, Schwarz SC, Storch A. Developmental perspectives on human midbrain-derived neural stem cells. Neurodegener Dis. 2006; 3(1-2):45-49.
  13. Storch A, Csoti I, Eggert K, et al. Intrathecal application of autologous bone marrow cell preparations in Parkinsonian syndromes. 2012; 27(12):1552-1555.
  14. Blue Cross and Blue Shield Association. Fetal mesencephalic transplantation for the treatment of Parkinson’s disease. TEC Assessment, 1995; 10(1).
  15. Blue Cross and Blue Shield Association. Embryonic mesencephalic transplantation for the treatment of Parkinson’s disease. TEC Assessment, 2001; 16(8).
  16. Brundin P, Kalia L, Olsen A; et al. International Parkinson and Movement Disorder Society (MDS) Position Paper - Use of stem cell therapies for Parkinson's disease. January 2021. Available at: https://www.movementdisorders.org/MDS/News/News--Notices/News-Release---Stem-Cell-Therapies/MDS-Position-Paper-Use-of-Stem-Cell-Therapies-for-Parkinsons-Disease.htm. Accessed on July 05, 2021.
  17. Fox SH, Katzenschlager R, Lim SY, et al. The Movement Disorder Society evidence-based medicine review update: treatments for the motor symptoms of Parkinson's disease. Mov Disord. 2011; 26 Suppl 3:S2-S41.
  18. Hallet M, Litvan I. Evaluation of surgery for Parkinson’s disease: a report of the therapeutics and technology assessment subcommittee of the American Academy of Neurology. Neurology. 1999; 53(9):1910-1921.
  19. International Parkinson and Movement Disorder Society. Available at: http://www.movementdisorders.org. Accessed on July 05, 2021.
  20. National Institute of Health. National Human Genome Research Institute. Learning about Parkinson’s. Updated April 29, 2020. Available at: https://www.genome.gov/Genetic-Disorders/Parkinsons-Disease. Accessed on July 05, 2021.
  21. National Institute of Neurological Disorders and Stroke (NINDS). Parkinson’s Disease Information Page. Available at: https://www.ninds.nih.gov/Disorders/All-Disorders/Parkinsons-Disease-Information-Page. Accessed on July 05, 2021.
  22. National Library of Medicine. Parkinson’s Disease. Updated February 27, 2020. Available at: http://www.nlm.nih.gov/medlineplus/parkinsonsdisease.html. 

Coding Section

Codes Number Description
CPT 64999 Unlisted procedure, nervous system (when specified as adrenal tissue transplant to brain, fetal mesencephalic transplant or fetal xenograft)
HCPCS  S2103 Adrenal tissue transplant to brain
ICD-9 Diagnosis  332.0-332.1 Parkinson's disease
ICD-10-CM (effective 10/01/15) G20 Parkinson's disease
  G21.0-G21.9 Secondary parkinsonism

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive. 

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross Blue Shield Association technology assessment program (TEC) and other nonaffiliated technology evaluation centers, reference to federal regulations, other plan medical policies and accredited national guidelines.

"Current Procedural Terminology © American Medical Association. All Rights Reserved" 

History From 2024 Forward  

01012024  NEW POLICY

03/27/2024 Annual review, no change to policy intent.

Complementary Content