Using T-Cell Alloreactivity and Chimerism to Guide Immunosuppression Minimization in Intestinal Transplantation

Inclusion Criteria: * All patients actively listed as candidates for intestinal or multi-visceral transplant at the study site; while all patients who are actively listed in United Network for Organ Sharing (UNOS) for intestinal and/or multi-visceral transplantation, including those who have previously received a multi-visceral transplant and are re-listed, are eligible for participation, the following are examples of listing criteria suitable for enrollment in this clinical trial: * Short Bowel Syndrome (SBS) due to: * Trauma (multiple resections/explorations and/or vascular abdominal trauma superior mesenteric artery (SMA) / superior mesenteric vein (SMV) injuries) * Gastroschisis * Volvulus * Necrotizing Enterocolitis * Intestinal Atresia * Crohn's Disease * Hirschprung's Disease * Chronic Intestinal Pseudo-Obstruction * Malabsorption: * Microvillus Inclusion Disease * Tufting Enteropathy * Complete portomesenteric thrombosis with cirrhosis * Slow-growing, low-malignancy potential tumors infiltrating mesenteric root: * Gardner's Syndrome * Familial Adenomatous Polyposis * Desmoid Tumor with Intra-Abdominal Infiltration * Endocrine Tumors * Re-transplant candidates who lost the first graft to rejection or patients who have higher risk of toxicity from chronic long term immunosuppression (i.e., patients with chronic kidney disease) * Patient commits to planned follow up at a study site for the 48-month duration of study procedures * Age ≥18 years old and ≤65 years old * Subjects or capable of signing the informed consent document themselves Exclusion Criteria: * Active systemic infection with hemodynamic instability and/or sepsis * Patients with known immunodeficiency syndrome * Carcinoma with metastasis (except neuro-endocrine tumors, even in the presence of metastasis these patients may undergo multivisceral/cluster transplantation) * Severe cardiovascular and/or respiratory instability, as defined by requirement of pressors or ventilator * Severe cerebral edema, with radiologic findings of effaced sulci and/or herniation * Poorly controlled hypertension (systolic blood pressure \> 170 on at least 2 occasions), diabetes mellitus (HbA1c \> 8), or uncontrollable seizure disorders * Age \> 65 years * Documented history of non-compliance with medical therapy and follow-up * Substance addiction in the last six months * Psychosocial Instability: absence of a consistent reliable social support system * Significant or active psychiatric disorder associated with the inability to cooperate or comply with medical therapy * In the judgement of the clinical team, severely limited functional status with poor rehabilitation potential * Multi-organ failure and preceding CD34+ infusion * Pre formed panel reactive antibodies (PRA) mean fluorescein intensity (MFI) \> 5000 by Luminex * Patients who are pregnant or breast-feeding or intend to get pregnant during the study period * Patients who have developed moderate or severe rejection before post-transplant day 11 * Vulnerable populations, such as incarcerated or institutionalized individuals * Subjects with clinical features suggestive of GVHD * Subjects who are hemodynamically unstable (i.e., requiring vasopressor support) * Female subjects of childbearing age and male patients who are not using and/or unwilling to use an effective method of birth control for the duration of the trial activities * History of previous hematopoietic progenitor cell (HPC) infusion or transplant of any kind. Note: Human leukocyte antigen (HLA) mismatch will not be one of the exclusion criteria